Hendrik Luesch

Hendrik Luesch, Ph.D.

Professor And Chair, Debbie And Sylvia DeSantis Chair In Natural Products Drug Discovery And Development

Department: Medicinal Chemistry
Business Phone: (352) 273-7738
Business Email: luesch@cop.ufl.edu

About Hendrik Luesch

Hendrik Luesch, Ph.D., a professor of medicinal chemistry, received his Diplom in Chemistry at the University of Siegen (Germany) in 1997. He attended the University of Hawaii at Manoa to study marine natural products chemistry and obtained his Ph.D. in Chemistry under the supervision of Professor Richard E. Moore in 2002. He then undertook three years of postdoctoral studies as an Irving S. Sigal Fellow at The Scripps Research Institute in La Jolla working with Professor Peter G. Schultz in the area of functional genomics and chemical biology. In 2005 he joined the faculty of the Department of Medicinal Chemistry at the University of Florida as an assistant professor and was tenured and promoted to associate professor in 2010 and to full professor in 2015. He combines his interest in marine natural products chemistry with genomics and proteomics approaches for the discovery and characterization of potential drugs and molecular drug targets.

Research Profile

Dr. Luesch’s multidisciplinary research program at the interface of chemistry and biology combines classical natural products chemistry with high-throughput screening and chemical genomics. It involves most aspects of drug discovery ranging from the collection of promising marine organisms, bioassay development, NMR spectroscopic structure determination, total synthesis, mechanism-of-action studies, and pharmacology, up to the preclinical and clinical development of candidate molecules. His lab is producing a small but increasing pipeline of bioactive compounds that are at various developmental stages. He also uses functional genomics approaches to identify and characterize genes associated with disease processes, especially cancer.

Publications

2020
Ahp-Cyclodepsipeptide Inhibitors of Elastase: Lyngbyastatin 7 Stability, Scalable Synthesis, and Focused Library Analysis.
ACS medicinal chemistry letters. 11(4):419-425 [DOI] 10.1021/acsmedchemlett.9b00473. [PMID] 32292544.
2020
Yohimbine as a Starting Point to Access Diverse Natural Product-Like Agents with Re-programmed Activities against Cancer-Relevant GPCR Targets.
Bioorganic & medicinal chemistry. 28(14) [DOI] 10.1016/j.bmc.2020.115546. [PMID] 32616180.
2020
Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity.
Beilstein journal of organic chemistry. 16:2663-2670 [DOI] 10.3762/bjoc.16.216. [PMID] 33178356.
2020
Tutuilamides A-C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.
ACS chemical biology. 15(3):751-757 [DOI] 10.1021/acschembio.9b00992. [PMID] 31935054.
2020
Targeting eukaryotic proteases for natural products-based drug development.
Natural product reports. 37(6):827-860 [DOI] 10.1039/c9np00060g. [PMID] 32519686.
2020
Targeting and extending the eukaryotic druggable genome with natural products.
Natural product reports. 37(6):744-746 [DOI] 10.1039/d0np90021d. [PMID] 32525143.
2020
Seaweed natural products modify the host inflammatory response via Nrf2 signaling and alter colon microbiota composition and gene expression.
Free radical biology & medicine. 146:306-323 [DOI] 10.1016/j.freeradbiomed.2019.09.013. [PMID] 31536771.
2020
Preventing Morphine-Seeking Behavior through the Re-Engineering of Vincamine’s Biological Activity.
Journal of medicinal chemistry. 63(10):5119-5138 [DOI] 10.1021/acs.jmedchem.9b01924. [PMID] 31913038.
2020
Ahp-Cyclodepsipeptides as tunable inhibitors of human neutrophil elastase and kallikrein 7: Total synthesis of tutuilamide A, serine protease selectivity profile and comparison with lyngbyastatin 7.
Bioorganic & medicinal chemistry. 28(23) [DOI] 10.1016/j.bmc.2020.115756. [PMID] 33002682.
2020
Largazole is a Brain-Penetrant Class I HDAC Inhibitor with Extended Applicability to Glioblastoma and CNS Diseases.
ACS chemical neuroscience. 11(13):1937-1943 [DOI] 10.1021/acschemneuro.0c00093. [PMID] 32559056.
2020
Discovery of new pyrimidine-5-carbonitrile derivatives as anticancer agents targeting EGFRWT and EGFRT790M.
Organic & biomolecular chemistry. 18(38):7608-7634 [DOI] 10.1039/d0ob01557a. [PMID] 32959865.
2020
Discovery, Total Synthesis, and SAR of Anaenamides A and B: Anticancer Cyanobacterial Depsipeptides with a Chlorinated Pharmacophore.
Organic letters. 22(11):4235-4239 [DOI] 10.1021/acs.orglett.0c01281. [PMID] 32418432.
2020
Dolastatin 15 from a Marine Cyanobacterium Suppresses HIF-1α Mediated Cancer Cell Viability and Vascularization.
Chembiochem : a European journal of chemical biology. 21(16):2356-2366 [DOI] 10.1002/cbic.202000180. [PMID] 32237262.
2020
Natural products as modulators of eukaryotic protein secretion.
Natural product reports. 37(5):717-736 [DOI] 10.1039/c9np00066f. [PMID] 32067014.
2020
High-throughput gene screen reveals modulators of nuclear shape.
Molecular biology of the cell. 31(13):1392-1402 [DOI] 10.1091/mbc.E19-09-0520. [PMID] 32320319.
2020
Fungal Epithiodiketopiperazines Carrying α,β-Polysulfide Bridges from Penicillium steckii YE, and Their Chemical Interconversion.
Chembiochem : a European journal of chemical biology. [DOI] 10.1002/cbic.202000403. [PMID] 32816319.
2019
Total Synthesis of Endolides A and B
Synlett. 30(20):2279-2284 [DOI] 10.1055/s-0037-1610736.
2019
Isolation, Structure Elucidation and Biological Evaluation of Lagunamide D: A New Cytotoxic Macrocyclic Depsipeptide from Marine Cyanobacteria.
Marine drugs. 17(2) [DOI] 10.3390/md17020083. [PMID] 30717076.
2019
Discovery of Amantamide, a Selective CXCR7 Agonist from Marine Cyanobacteria.
Organic letters. 21(6):1622-1626 [DOI] 10.1021/acs.orglett.9b00163. [PMID] 30779584.
2019
Discovery and Total Synthesis of Doscadenamide A: A Quorum Sensing Signaling Molecule from a Marine Cyanobacterium.
Organic letters. 21(18):7274-7278 [DOI] 10.1021/acs.orglett.9b02525. [PMID] 31414826.
2019
New methods for isolation and structure determination of natural products.
Natural product reports. 36(7):942-943 [DOI] 10.1039/c9np90023c. [PMID] 31250867.
2019
Chemical and Metagenomic Studies of the Lethal Black Band Disease of Corals Reveal Two Broadly Distributed, Redox-Sensitive Mixed Polyketide/Peptide Macrocycles.
Journal of natural products. 82(1):111-121 [DOI] 10.1021/acs.jnatprod.8b00804. [PMID] 30636420.
2019
Apratoxin S4 Inspired by a Marine Natural Product, a New Treatment Option for Ocular Angiogenic Diseases.
Investigative ophthalmology & visual science. 60(8):3254-3263 [DOI] 10.1167/iovs.19-26936. [PMID] 31361305.
2019
Advances in exploring the therapeutic potential of marine natural products.
Pharmacological research. 147 [DOI] 10.1016/j.phrs.2019.104373. [PMID] 31351913.
2019
Development of apratoxin S10 (Apra S10) as an anti-pancreatic cancer agent and its preliminary evaluation in an orthotopic patient-derived xenograft (PDX) model.
Investigational new drugs. 37(2):364-374 [DOI] 10.1007/s10637-018-0647-0. [PMID] 30073464.
2018
Process Development and Scale-up Total Synthesis of Largazole, a Potent Class I Histone Deacetylase Inhibitor
Organic Process Research and Development. 22(2):190-199 [DOI] 10.1021/acs.oprd.7b00352.
2018
Total Synthesis of Asperphenins A and B.
Organic letters. 20(19):6170-6173 [DOI] 10.1021/acs.orglett.8b02652. [PMID] 30232896.
2018
The nucleus is irreversibly shaped by motion of cell boundaries in cancer and non-cancer cells.
Journal of cellular physiology. 233(2):1446-1454 [DOI] 10.1002/jcp.26031. [PMID] 28542912.
2018
The adaptive regulation of thiamine pyrophosphokinase-1 facilitates malignant growth during supplemental thiamine conditions.
Oncotarget. 9(83):35422-35438 [DOI] 10.18632/oncotarget.26259. [PMID] 30459934.
2018
Structural Diversity and Anticancer Activity of Marine-Derived Elastase Inhibitors: Key Features and Mechanisms Mediating the Antimetastatic Effects in Invasive Breast Cancer.
Chembiochem : a European journal of chemical biology. 19(8):815-825 [DOI] 10.1002/cbic.201700627. [PMID] 29405541.
2018
Rational engineering of Streptomyces albus J1074 for the overexpression of secondary metabolite gene clusters.
Microbial cell factories. 17(1) [DOI] 10.1186/s12934-018-0874-2. [PMID] 29454348.
2018
Photosynthetic Production of Sunscreen Shinorine Using an Engineered Cyanobacterium.
ACS synthetic biology. 7(2):664-671 [DOI] 10.1021/acssynbio.7b00397. [PMID] 29304277.
2018
Discovery of new A- and B-type laxaphycins with synergistic anticancer activity.
Bioorganic & medicinal chemistry. 26(9):2310-2319 [DOI] 10.1016/j.bmc.2018.03.022. [PMID] 29606488.
2018
High-Yield Production of Herbicidal Thaxtomins and Thaxtomin Analogs in a Nonpathogenic Streptomyces Strain.
Applied and environmental microbiology. 84(11) [DOI] 10.1128/AEM.00164-18. [PMID] 29602787.
2018
Discovery, Synthesis, Pharmacological Profiling, and Biological Characterization of Brintonamides A-E, Novel Dual Protease and GPCR Modulators from a Marine Cyanobacterium.
Journal of medicinal chemistry. 61(14):6364-6378 [DOI] 10.1021/acs.jmedchem.8b00885. [PMID] 30015488.
2018
Correction to Apratoxin E, a Cytotoxic Peptolide from a Guamanian Collection of the Marine Cyanobacterium Lyngbya bouillonii.
Journal of natural products. 81(1) [DOI] 10.1021/acs.jnatprod.7b00982. [PMID] 29257686.
2018
An Efficient Buchwald-Hartwig/Reductive Cyclization for the Scaffold Diversification of Halogenated Phenazines: Potent Antibacterial Targeting, Biofilm Eradication, and Prodrug Exploration.
Journal of medicinal chemistry. 61(9):3962-3983 [DOI] 10.1021/acs.jmedchem.7b01903. [PMID] 29638121.
2018
A Complementary Chemical and Genomic Screening Approach for Druggable Targets in the Nrf2 Pathway and Small Molecule Inhibitors to Overcome Cancer Cell Drug Resistance.
ACS chemical biology. 13(5):1189-1199 [DOI] 10.1021/acschembio.7b01025. [PMID] 29565554.
2018
Isolation and Characterization of Anaephenes A-C, Alkylphenols from a Filamentous Cyanobacterium ( Hormoscilla sp., Oscillatoriales).
Journal of natural products. 81(12):2716-2721 [DOI] 10.1021/acs.jnatprod.8b00650. [PMID] 30489078.
2018
Apratyramide, a Marine-Derived Peptidic Stimulator of VEGF-A and Other Growth Factors with Potential Application in Wound Healing.
ACS chemical biology. 13(1):91-99 [DOI] 10.1021/acschembio.7b00827. [PMID] 29205032.
2017
Kempopeptin C, a Novel Marine-Derived Serine Protease Inhibitor Targeting Invasive Breast Cancer.
Marine drugs. 15(9) [DOI] 10.3390/md15090290. [PMID] 28926939.
2017
Synthesis and biological evaluation of largazole zinc-binding group analogs.
Bioorganic & medicinal chemistry. 25(12):3077-3086 [DOI] 10.1016/j.bmc.2017.03.071. [PMID] 28416100.
2017
Poly(N-(2-Hydroxypropyl)-Methacrylamide)-Valproic Acid Conjugates As Block Copolymer Nanocarriers
Polymer Chemistry. 8(34):4983-4987 [DOI] 10.1039/c7py00196g.
2017
Poly(N-(2-Hydroxypropyl) Methacrylamide)-Valproic Acid Conjugates as Block Copolymer Nanocarriers.
Polymer chemistry. 8(34):4983-4987 [DOI] 10.1039/C7PY00196G. [PMID] 28959359.
2017
Grassystatins D-F, Potent Aspartic Protease Inhibitors from Marine Cyanobacteria as Potential Antimetastatic Agents Targeting Invasive Breast Cancer.
Journal of natural products. 80(11):2969-2986 [DOI] 10.1021/acs.jnatprod.7b00551. [PMID] 29087712.
2017
Correction to “Apratoxin S10, a Dual Inhibitor of Angiogenesis and Cancer Cell Growth To Treat Highly Vascularized Tumors”.
ACS medicinal chemistry letters. 8(12) [DOI] 10.1021/acsmedchemlett.7b00498. [PMID] 29266134.
2017
Cyanobacterial Sfp-type phosphopantetheinyl transferases functionalize carrier proteins of diverse biosynthetic pathways.
Scientific reports. 7(1) [DOI] 10.1038/s41598-017-12244-3. [PMID] 28928426.
2017
A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis.
Scientific reports. 7(1) [DOI] 10.1038/s41598-017-01045-3. [PMID] 28515440.
2017
A Tryptoline Ring-Distortion Strategy Leads to Complex and Diverse Biologically Active Molecules from the Indole Alkaloid Yohimbine.
Chemistry (Weinheim an der Bergstrasse, Germany). 23(18):4327-4335 [DOI] 10.1002/chem.201604795. [PMID] 27900785.
2017
Apratoxin S10, a Dual Inhibitor of Angiogenesis and Cancer Cell Growth To Treat Highly Vascularized Tumors.
ACS medicinal chemistry letters. 8(10):1007-1012 [DOI] 10.1021/acsmedchemlett.7b00192. [PMID] 29057042.
2016
Caldoramide, a Modified Pentapeptide from the Marine Cyanobacterium Caldora penicillata.
Journal of natural products. 79(7):1867-71 [DOI] 10.1021/acs.jnatprod.6b00203. [PMID] 27380142.
2016
Correction to Caylobolide B, a Macrolactone from Symplostatin 1-Producing Marine Cyanobacteria Phormidium spp. from Florida.
Journal of natural products. 79(2) [DOI] 10.1021/acs.jnatprod.6b00120. [PMID] 26885760.
2016
CUB domain-containing protein 1 and the epidermal growth factor receptor cooperate to induce cell detachment.
Breast cancer research : BCR. 18(1) [DOI] 10.1186/s13058-016-0741-1. [PMID] 27495374.
2016
Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria.
Chemistry (Weinheim an der Bergstrasse, Germany). 22(24):8158-66 [DOI] 10.1002/chem.201600674. [PMID] 27139508.
2016
Pitiamides A and B, Multifunctional Fatty Acid Amides from Marine Cyanobacteria.
Planta medica. 82(9-10):897-902 [DOI] 10.1055/s-0042-105157. [PMID] 27135625.
2016
Structure-Activity Relationships of a Diverse Class of Halogenated Phenazines That Targets Persistent, Antibiotic-Tolerant Bacterial Biofilms and Mycobacterium tuberculosis.
Journal of medicinal chemistry. 59(8):3808-25 [DOI] 10.1021/acs.jmedchem.5b02004. [PMID] 27018907.
2016
Tasiamide F, a potent inhibitor of cathepsins D and E from a marine cyanobacterium.
Bioorganic & medicinal chemistry. 24(15):3276-82 [DOI] 10.1016/j.bmc.2016.04.062. [PMID] 27211244.
2016
Total Synthesis and Biological Evaluation of Apratoxin E and Its C30 Epimer: Configurational Reassignment of the Natural Product.
Organic letters. 18(20):5400-5403 [DOI] 10.1021/acs.orglett.6b02780. [PMID] 27723359.
2016
Total Synthesis of the Potent Marine-Derived Elastase Inhibitor Lyngbyastatin 7 and in Vitro Biological Evaluation in Model Systems for Pulmonary Diseases.
The Journal of organic chemistry. 81(2):532-44 [DOI] 10.1021/acs.joc.5b02386. [PMID] 26709602.
2015
Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures, and Mycobacterium tuberculosis.
Angewandte Chemie (International ed. in English). 54(49):14819-23 [DOI] 10.1002/anie.201508155. [PMID] 26480852.
2015
Caldora penicillata gen. nov., comb. nov. (cyanobacteria), a pantropical marine species with biomedical relevance.
Journal of phycology. 51(4):670-81 [PMID] 26327714.
View on: PubMed
2015
Targeted natural products discovery from marine cyanobacteria using combined phylogenetic and mass spectrometric evaluation.
Journal of natural products. 78(3):486-92 [DOI] 10.1021/np500931q. [PMID] 25635943.
2015
Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum Cytotoxicity from a Guamanian Marine Cyanobacterium.
Journal of natural products. 78(8):1957-62 [DOI] 10.1021/acs.jnatprod.5b00293. [PMID] 26204500.
2015
Biological targets and mechanisms of action of natural products from marine cyanobacteria.
Natural product reports. 32(3):478-503 [DOI] 10.1039/c4np00104d. [PMID] 25571978.
2015
Discovery of ML358, a Selective Small Molecule Inhibitor of the SKN-1 Pathway Involved in Drug Detoxification and Resistance in Nematodes.
ACS chemical biology. 10(8):1871-9 [DOI] 10.1021/acschembio.5b00304. [PMID] 25946346.
2015
A dive into membrane dynamics with sponge peptides.
Chemistry & biology. 22(5):565-7 [DOI] 10.1016/j.chembiol.2015.05.003. [PMID] 26000744.
2014
Evaluation of class I HDAC isoform selectivity of largazole analogues.
Bioorganic & medicinal chemistry letters. 24(16):3728-31 [DOI] 10.1016/j.bmcl.2014.07.006. [PMID] 25070421.
2014
Grassypeptolides as natural inhibitors of dipeptidyl peptidase 8 and T-cell activation.
Chembiochem : a European journal of chemical biology. 15(6):799-804 [DOI] 10.1002/cbic.201300762. [PMID] 24591193.
2014
Improved total synthesis and biological evaluation of potent apratoxin S4 based anticancer agents with differential stability and further enhanced activity.
Journal of medicinal chemistry. 57(7):3011-29 [DOI] 10.1021/jm4019965. [PMID] 24660812.
2014
Improved Total Synthesis and Biological Evaluation of Potent Apratoxin S4 Based Anticancer Agents With Enhanced Activity
Planta Medica. 80(10)
2014
Largazole pharmacokinetics in rats by LC-MS/MS.
Marine drugs. 12(3):1623-40 [DOI] 10.3390/md12031623. [PMID] 24658499.
2014
Modulation of Activity Profiles for Largazole-Based HDAC Inhibitors through Alteration of Prodrug Properties.
ACS medicinal chemistry letters. 5(8):905-10 [DOI] 10.1021/ml500170r. [PMID] 25147612.
2013
Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms.
Oncogene. 32(10):1316-29 [DOI] 10.1038/onc.2012.138. [PMID] 22543582.
2013
In vitro and in vivo characterization of a tunable dual-reactivity probe of the Nrf2-ARE pathway.
ACS chemical biology. 8(8):1764-74 [DOI] 10.1021/cb4000103. [PMID] 23773140.
2013
Modular strategies for structure and function employed by marine cyanobacteria: characterization and synthesis of pitinoic acids.
Organic letters. 15(16):4050-3 [DOI] 10.1021/ol401396u. [PMID] 23915229.
2013
Potent elastase inhibitors from cyanobacteria: structural basis and mechanisms mediating cytoprotective and anti-inflammatory effects in bronchial epithelial cells.
Journal of medicinal chemistry. 56(3):1276-90 [DOI] 10.1021/jm3017305. [PMID] 23350733.
2013
Seaweed extracts and unsaturated fatty acid constituents from the green alga Ulva lactuca as activators of the cytoprotective Nrf2-ARE pathway.
Free radical biology & medicine. 57:141-53 [DOI] 10.1016/j.freeradbiomed.2012.12.019. [PMID] 23291594.
2013
Total synthesis and biological evaluation of grassypeptolide A.
Chemistry (Weinheim an der Bergstrasse, Germany). 19(21):6774-84 [DOI] 10.1002/chem.201203667. [PMID] 23536467.
2013
Cultivated sea lettuce is a multiorgan protector from oxidative and inflammatory stress by enhancing the endogenous antioxidant defense system.
Cancer prevention research (Philadelphia, Pa.). 6(9):989-99 [DOI] 10.1158/1940-6207.CAPR-13-0014. [PMID] 24005795.
2012
Chemistry and Biology of Novel Cyanobacterial Secondary Metabolites From Guam
Planta Medica. 78
2012
Cyanobacterial peptides as a prototype for the design of potent β-secretase inhibitors and the development of selective chemical probes for other aspartic proteases.
Journal of medicinal chemistry. 55(23):10749-65 [DOI] 10.1021/jm301630s. [PMID] 23181502.
2012
Discovery and mechanism of natural products as modulators of histone acetylation.
Current drug targets. 13(8):1029-47 [PMID] 22594471.
View on: PubMed
2012
Marine cyanobacterial fatty acid amides acting on cannabinoid receptors.
Chembiochem : a European journal of chemical biology. 13(18):2676-81 [DOI] 10.1002/cbic.201200502. [PMID] 23143757.
2012
Novel Elastase Inhibitors From Marine Cyanobacteria: Structural Diversity, Target-Bound Crystal Structures and Cellular Effects
Planta Medica. 78
2012
Total synthesis of grassystatin A, a probe for cathepsin E function.
Bioorganic & medicinal chemistry. 20(15):4774-80 [DOI] 10.1016/j.bmc.2012.05.077. [PMID] 22748705.
2012
Largazole: from discovery to broad-spectrum therapy.
Natural product reports. 29(4):449-56 [DOI] 10.1039/c2np00066k. [PMID] 22334030.
2011
Systematic Chemical Mutagenesis Identifies a Potent Novel Apratoxin A/E Hybrid with Improved in Vivo Antitumor Activity.
ACS medicinal chemistry letters. 2(11):861-865 [PMID] 22081789.
View on: PubMed
2011
Porpoisamides A and B, two novel epimeric cyclic depsipeptides from a Florida Keys collection of Lyngbya sp.
Bioorganic & medicinal chemistry. 19(22):6576-80 [DOI] 10.1016/j.bmc.2011.05.051. [PMID] 21705224.
2011
Pitiprolamide, a proline-rich dolastatin 16 analogue from the marine cyanobacterium Lyngbya majuscula from Guam.
Journal of natural products. 74(1):109-12 [DOI] 10.1021/np1006839. [PMID] 21138309.
2011
Pitipeptolides C-F, antimycobacterial cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula from Guam.
Phytochemistry. 72(16):2068-74 [DOI] 10.1016/j.phytochem.2011.07.014. [PMID] 21843895.
2011
Marine natural products: a new wave of drugs?
Future medicinal chemistry. 3(12):1475-89 [DOI] 10.4155/fmc.11.118. [PMID] 21882941.
2011
Malyngamide 3 and cocosamides A and B from the marine cyanobacterium Lyngbya majuscula from Cocos Lagoon, Guam.
Journal of natural products. 74(4):871-6 [DOI] 10.1021/np1008015. [PMID] 21341718.
2011
Veraguamides A-G, cyclic hexadepsipeptides from a dolastatin 16-producing cyanobacterium Symploca cf. hydnoides from Guam.
Journal of natural products. 74(5):917-27 [DOI] 10.1021/np200076t. [PMID] 21446699.
2011
In Vitro and In Vivo Osteogenic Activity of Largazole.
ACS medicinal chemistry letters. 2(3):248-251 [PMID] 21666868.
View on: PubMed
2011
Combination therapy targeting cancer metabolism.
Medical hypotheses. 76(2):169-72 [DOI] 10.1016/j.mehy.2010.09.008. [PMID] 20947261.
2011
Combination therapy for renal cell cancer: what are possible options?
Oncology. 81(3-4):220-9 [DOI] 10.1159/000333470. [PMID] 22085914.
2011
Can we develop effective combination antiangiogenic therapy for patients with hepatocellular carcinoma?
Oncology reviews. 5(3):177-184 [PMID] 21949574.
View on: PubMed
2011
Biological effects of Byrsocarpus coccineus in vitro.
Pharmaceutical biology. 49(2):152-60 [DOI] 10.3109/13880209.2010.504967. [PMID] 21110733.
2011
Bioactive Modified Peptides From Marine Cyanobacteria
Biopolymers. 96
2011
Lyngbyoic acid, a “tagged” fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa.
Molecular bioSystems. 7(4):1205-16 [DOI] 10.1039/c0mb00180e. [PMID] 21258753.
2010
Weapons in disguise–activating mechanisms and protecting group chemistry in nature.
Chemistry (Weinheim an der Bergstrasse, Germany). 16(44):13020-9 [DOI] 10.1002/chem.201001562. [PMID] 20931575.
2010
Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-dependent gene expression.
Nature cell biology. 12(8):758-67 [DOI] 10.1038/ncb2080. [PMID] 20622870.
2010
Molassamide, a depsipeptide serine protease inhibitor from the marine cyanobacterium Dichothrix utahensis.
Journal of natural products. 73(3):459-62 [DOI] 10.1021/np900603f. [PMID] 20020755.
2010
Isolation and biological evaluation of 8-epi-malyngamide C from the Floridian marine cyanobacterium Lyngbya majuscula.
Journal of natural products. 73(3):463-6 [DOI] 10.1021/np900614n. [PMID] 20166701.
2010
Intramolecular modulation of serine protease inhibitor activity in a marine cyanobacterium with antifeedant properties.
Marine drugs. 8(6):1803-16 [DOI] 10.3390/md8061803. [PMID] 20631871.
2010
Cytotoxic halogenated macrolides and modified peptides from the apratoxin-producing marine cyanobacterium Lyngbya bouillonii from Guam.
Journal of natural products. 73(9):1544-52 [DOI] 10.1021/np1004032. [PMID] 20704304.
2010
Caylobolide B, a macrolactone from symplostatin 1-producing marine cyanobacteria Phormidium spp. from Florida.
Journal of natural products. 73(9):1606-9 [DOI] 10.1021/np100467d. [PMID] 20806908.
2010
Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor.
The Journal of pharmacology and experimental therapeutics. 335(2):351-61 [DOI] 10.1124/jpet.110.172387. [PMID] 20739454.
2010
A small-molecule inducer of the antioxidant response element.
Chemistry & biology. 17(5):537-47 [DOI] 10.1016/j.chembiol.2010.03.013. [PMID] 20534351.
2010
Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides.
The Journal of organic chemistry. 75(23):8012-23 [DOI] 10.1021/jo1013564. [PMID] 21047144.
2009
Largamides A-C, tiglic acid-containing cyclodepsipeptides with elastase-inhibitory activity from the marine cyanobacterium Lyngbya confervoides.
Planta medica. 75(5):528-33 [DOI] 10.1055/s-0029-1185332. [PMID] 19214948.
2009
Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of antioxidant defenses.
Free radical biology & medicine. 47(5):577-84 [DOI] 10.1016/j.freeradbiomed.2009.05.025. [PMID] 19486939.
2009
Phylogenetic and chemical diversity of three chemotypes of bloom-forming lyngbya species (Cyanobacteria: Oscillatoriales) from reefs of southeastern Florida.
Applied and environmental microbiology. 75(9):2879-88 [DOI] 10.1128/AEM.02656-08. [PMID] 19270119.
2009
Novel Natural Activators of the Antioxidant Response Element
Journal of the Neurological Sciences. 285
2009
Lyngbyastatins 8-10, elastase inhibitors with cyclic depsipeptide scaffolds isolated from the marine cyanobacterium Lyngbya semiplena.
Marine drugs. 7(4):528-38 [DOI] 10.3390/md7040528. [PMID] 20098596.
2009
Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation.
Journal of medicinal chemistry. 52(18):5732-47 [DOI] 10.1021/jm9009394. [PMID] 19715320.
2009
Tiglicamides A-C, cyclodepsipeptides from the marine cyanobacterium Lyngbya confervoides.
Phytochemistry. 70(17-18):2058-63 [DOI] 10.1016/j.phytochem.2009.09.010. [PMID] 19815244.
2009
Combinatorial strategies by marine cyanobacteria: symplostatin 4, an antimitotic natural dolastatin 10/15 hybrid that synergizes with the coproduced HDAC inhibitor largazole.
Chembiochem : a European journal of chemical biology. 10(10):1634-9 [DOI] 10.1002/cbic.200900192. [PMID] 19514039.
2009
Bioassay-guided isolation and identification of desacetylmicrocolin B from Lyngbya cf. polychroa.
Planta medica. 75(13):1427-30 [DOI] 10.1055/s-0029-1185675. [PMID] 19431099.
2009
Apratoxin a reversibly inhibits the secretory pathway by preventing cotranslational translocation.
Molecular pharmacology. 76(1):91-104 [DOI] 10.1124/mol.109.056085. [PMID] 19403701.
2009
Activation of the antioxidant response element by specific oxidized metabolites of linoleic acid.
Prostaglandins, leukotrienes, and essential fatty acids. 81(1):53-9 [DOI] 10.1016/j.plefa.2009.04.008. [PMID] 19481916.
2009
A natural products approach to drug discovery: probing modes of action of antitumor agents by genome-scale cDNA library screening.
Methods in molecular biology (Clifton, N.J.). 572:261-77 [DOI] 10.1007/978-1-60761-244-5_17. [PMID] 20694698.
2009
Construction and characterization of melanocortin-2 and -4 receptor chimeras.
Advances in experimental medicine and biology. 611:301-2 [PMID] 19400202.
View on: PubMed
2008
Total synthesis and molecular target of largazole, a histone deacetylase inhibitor.
Journal of the American Chemical Society. 130(26):8455-9 [DOI] 10.1021/ja8013727. [PMID] 18507379.
2008
Total structure determination of grassypeptolide, a new marine cyanobacterial cytotoxin.
Organic letters. 10(5):789-92 [DOI] 10.1021/ol702946d. [PMID] 18220404.
2008
Total Structure Determination of Grassypeptolide, a New Marine Cyanobacterial Cytotoxin
Organic Letters. 10:789-792 [DOI] 10.1021/0l702946d.
2008
Synthesis and activity of largazole analogues with linker and macrocycle modification.
Organic letters. 10(18):4021-4 [DOI] 10.1021/ol801532s. [PMID] 18707106.
2008
Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp.
Journal of the American Chemical Society. 130(6):1806-7 [DOI] 10.1021/ja7110064. [PMID] 18205365.
2008
Structure and Activity of Largazole, a Potent Antiproliferative Agent From the Floridian Marine Cyanobacterium Symploca Sp.
Journal of the American Chemical Society. 130 [DOI] 10.1021/ja710064S0002-7863(71)01006-0.
2008
Serine Protease Inhibitors From the Floridian Marine Cyanobacterium Lyngbya Confervoides
Planta Medica. 74:1037-1038
2008
Pompanopeptins a and B, New Cyclic Peptides From the Marine Cyanobacterium Lyngbya Confervoides
Tetrahedron. 64(18):4081-4089 [DOI] 10.1016/j.tet.2008.02.035.
2008
Kempopeptins A and B, serine protease inhibitors with different selectivity profiles from a marine cyanobacterium, Lyngbya sp.
Journal of natural products. 71(9):1625-9 [DOI] 10.1021/np8002172. [PMID] 18693761.
2008
Genome-wide overexpression screen for activators of antioxidant gene transcription.
Methods in molecular biology (Clifton, N.J.). 477:343-54 [DOI] 10.1007/978-1-60327-517-0_26. [PMID] 19082959.
2008
Dragonamides C and D, linear lipopeptides from the marine cyanobacterium brown Lyngbya polychroa.
Journal of natural products. 71(5):887-90 [DOI] 10.1021/np0706769. [PMID] 18393465.
2008
Bioactive Natural Products From Marine Cyanobacteria: New Structures and Modes of Action
Planta Medica. 74
2008
Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii.
Journal of natural products. 71(6):1113-6 [DOI] 10.1021/np700717s. [PMID] 18461997.
2008
Orgn 523-Total Synthesis of Largazole
. 236
2007
A genomic screen for activators of the antioxidant response element.
Proceedings of the National Academy of Sciences of the United States of America. 104(12):5205-10 [PMID] 17360324.
View on: PubMed
2007
Lyngbyastatin 4, a dolastatin 13 analogue with elastase and chymotrypsin inhibitory activity from the marine cyanobacterium Lyngbya confervoides.
Journal of natural products. 70(1):124-7 [PMID] 17253864.
View on: PubMed
2007
Lyngbyastatins 5-7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp.
Journal of natural products. 70(10):1593-600 [PMID] 17910513.
View on: PubMed
2006
Towards high-throughput characterization of small molecule mechanisms of action.
Molecular bioSystems. 2(12):609-20 [PMID] 17216042.
View on: PubMed
2006
A functional genomics approach to the mode of action of apratoxin A.
Nature chemical biology. 2(3):158-67 [PMID] 16474387.
View on: PubMed
2005
A genome-wide overexpression screen in yeast for small-molecule target identification.
Chemistry & biology. 12(1):55-63 [PMID] 15664515.
View on: PubMed
2003
Biosynthesis of 4-methylproline in cyanobacteria: cloning of nosE and nosF genes and biochemical characterization of the encoded dehydrogenase and reductase activities.
The Journal of organic chemistry. 68(1):83-91 [PMID] 12515465.
View on: PubMed
2003
Continuing studies on the cyanobacterium Lyngbya sp.: isolation and structure determination of 15-norlyngbyapeptin A and lyngbyabellin D.
Journal of natural products. 66(5):595-8 [PMID] 12762789.
View on: PubMed
2003
The molecular pharmacology of symplostatin 1: a new antimitotic dolastatin 10 analog.
International journal of cancer. 104(4):512-21 [PMID] 12584751.
View on: PubMed
2002
Lyngbyaloside B, a new glycoside macrolide from a Palauan marine cyanobacterium, Lyngbya sp.
Journal of natural products. 65(12):1945-8 [PMID] 12502348.
View on: PubMed
2002
New apratoxins of marine cyanobacterial origin from Guam and Palau.
Bioorganic & medicinal chemistry. 10(6):1973-8 [PMID] 11937357.
View on: PubMed
2002
Symplostatin 3, a new dolastatin 10 analogue from the marine cyanobacterium Symploca sp. VP452.
Journal of natural products. 65(1):16-20 [PMID] 11809057.
View on: PubMed
2002
The cyanobacterial origin of potent anticancer agents originally isolated from sea hares.
Current medicinal chemistry. 9(20):1791-806 [PMID] 12369878.
View on: PubMed
2002
Ulongamides A-F, new beta-amino acid-containing cyclodepsipeptides from Palauan collections of the marine cyanobacterium Lyngbya sp.
Journal of natural products. 65(7):996-1000 [PMID] 12141859.
View on: PubMed
2001
Total structure determination of apratoxin A, a potent novel cytotoxin from the marine cyanobacterium Lyngbya majuscula.
Journal of the American Chemical Society. 123(23):5418-23 [PMID] 11389621.
View on: PubMed
2001
Pitipeptolides A and B, new cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula.
Journal of natural products. 64(3):304-7 [PMID] 11277744.
View on: PubMed
2001
Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1.
Journal of natural products. 64(7):907-10 [PMID] 11473421.
View on: PubMed
2001
Dysideaprolines A-F and barbaleucamides A-B, novel polychlorinated compounds from a Dysidea species.
Journal of natural products. 64(9):1133-8 [PMID] 11575943.
View on: PubMed
2000
Apramides A-G, novel lipopeptides from the marine cyanobacterium Lyngbya majuscula.
Journal of natural products. 63(8):1106-12 [PMID] 10978206.
View on: PubMed
2000
Isolation and structure of the cytotoxin lyngbyabellin B and absolute configuration of lyngbyapeptin A from the marine cyanobacterium Lyngbya majuscula.
Journal of natural products. 63(10):1437-9 [PMID] 11076573.
View on: PubMed
2000
Isolation, structure determination, and biological activity of Lyngbyabellin A from the marine cyanobacterium lyngbya majuscula.
Journal of natural products. 63(5):611-5 [PMID] 10843570.
View on: PubMed
1999
Lyngbyastatin 2 and norlyngbyastatin 2, analogues of dolastatin G and nordolastatin G from the marine cyanobacterium Lyngbya majuscula.
Journal of natural products. 62(12):1702-6 [PMID] 10654420.
View on: PubMed
1999
Symplostatin 2: a dolastatin 13 analogue from the marine cyanobacterium Symploca hydnoides.
Journal of natural products. 62(4):655-8 [PMID] 10217737.
View on: PubMed
1999
Tumonoic acids, novel metabolites from a cyanobacterial assemblage of Lyngbya majuscula and Schizothrix calcicola.
Journal of natural products. 62(3):464-7 [PMID] 10096859.
View on: PubMed
1998
Symplostatin 1: A dolastatin 10 analogue from the marine cyanobacterium Symploca hydnoides.
Journal of natural products. 61(9):1075-7 [PMID] 9748368.
View on: PubMed

Grants

Jun 2020 ACTIVE
NMR console upgrade for structural biology and metabolomics
Role:
Funding: NATL INST OF HLTH OD
Sep 2019 ACTIVE
Novel Targeted Anticancer Agents from Marine Cyanobacteria
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Aug 2019 – Mar 2020
Potential Anticancer Drug Leads from the Marine Sponges Collected off the Coast of Surigao City
Role: Principal Investigator
Funding: MINDANAO STATE UNIVERSITY via SCIENCE EDUCATION INSTITUTE
Dec 2018 – Nov 2019
Identifying CxCR4 Receptor Agonists to Improve Diabetic Healing
Role: Project Manager
Funding: UNIVERSITY OF COLORADO DENVER via NATL INST OF HLTH NIDDK
Dec 2018 ACTIVE
Small Molecule Discovery for Particulate Guanylyl Cyclase Receptor B Enhancers
Role: Project Manager
Funding: MAYO CLINIC via NATL INST OF HLTH NIA
Aug 2018 ACTIVE
MRI: Acquisition of an X-Ray Diffractometer for Next Generation Functional Molecules and Materials
Role:
Funding: NATL SCIENCE FOU
Jul 2018 ACTIVE
OR-DRPD-ROF2018: A C. elegans based drug discovery platform for modulators of re-mRNA processing
Role:
Funding: UF RESEARCH
Jul 2018 ACTIVE
Alkaloid Ring Distortion: A Platform for New Cancer Therapies
Role: Project Manager
Funding: AMER CANCER SOC
Sep 2017 – Aug 2020
Utilization of Phenotypic Precision Medicine to Identify Optimal Drug Combinations for the Treatment of Hepatocellular Carcinoma
Role:
Funding: NATL INST OF HLTH NCATS
Dec 2016 ACTIVE
UF PASS: Regulation of exercise transducers
Role:
Funding: NATL INST OF HLTH NIA
Sep 2016 ACTIVE
Development of Complex Natural Product Libraries and Multidimensional Anticancer Screening Platforms
Role: Mentor
Funding: NATL INST OF HLTH NCI
Jul 2016 – Jun 2018
NOVEL SYNTHETIC APRATOXINS ACTING THROUGH A NEW MECHANISM ASAN ALTERNATIVE TREATMENT OF CANCERS WITH ACTIVATED GROWTH…
Role: Principal Investigator
Funding: OCALA ROYAL DAMES FOR CANCER RESEARCH
Jun 2014 – May 2017
Novel Therapeutics for activation of the antioxidant res
Role: Project Manager
Funding: UF DSR OPPORTUNITY FUND
Dec 2013 – Nov 2015
Chemistry and Biology of Apratoxins
Role: Principal Investigator
Funding: FL DEPT OF HLTH BANKHEAD-COLEY CANCER RE
Mar 2013 – Aug 2019
Novel Targeted Anticancer Agents from Marine Cyanobacteria
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Mar 2011 – Feb 2016
Mitochondrial Oxidative Stress in the Retinal Pigment Ep
Role: Project Manager
Funding: NATL INST OF HLTH NEI

Patents

Published March 2010
Macrocyclic Compounds, Protease Inhibition, and Methods of Treatment
#US2011-0124569A1
Published December 2010
Macrocyclic Compounds and Methods of Treatment (New App.)
#2011-0123644 A1
Published May 2011
Apratoxin Therapetuic Agents: Mechanism and Methods of Treatment
#US 2011-0294720 A1
Issued March 2012
Macrocyclic Compounds and Methods of Treatment
#8,129,418
Published November 2012
Macrocyclic Compounds and Methods of Treatment
#US2013-0281497 A1
Issued January 2013
Macrocyclic Compounds and Methods of Treatment (DIV of 12606)
#8,357,708
Issued October 2013
Structure and Protease Activity of Grassystatins
#8,569,245
Issued June 2014
Methods of Preparation of Macrocyclic Compounds
#8,759,512
Published August 2014
Macrocyclic Compounds
#US2015-0038404 A1
Issued May 2015
Macrocyclic Compounds and Methods of Treatment (DIV of UF#12606)
#9,023,875
Issued June 2015
Macrocyclic Antiproliferation Agents and Methods of Treatment
#9,051,350
Published October 2015
Macrocyclic Compounds and Methods of Treatment
#US 2016/0106720
Published November 2015
Potent New Synthetic Apratoxins
#US-2016-0060299-A1
Issued November 2015
Macrocyclic Compounds and Methods of Treatment
#9,181,304
Published August 2016
Macrocyclic Therapeutic Agents, Methods of Manufacture, and Methods of Treatment
#US-2017-0057996
Issued November 2016
Combination Compositions and Methods of Treatment
#9,492,434
Issued August 2017
Seaweed Extracts, Unsaturated Aldehydes, and Methods of Treatment
#9,730,970
Issued November 2017
Macrocyclic Compounds and Methods of Treatment
#9,815,852
Issued July 2018
Seaweed Extracts, Unsaturated Fatty Acids, and Methods of Treatment
#10,010,569

Education

Postdoctoral Fellow
2002-2005 · The Scripps Research Institute
Ph.D.
2002 · University of Hawaii at Manoa
Diplom in Chemistry
1997 · University of Siegen

Teaching Profile

Courses Taught
2009-2020
PHA7980 Research for Doctoral Dissertation
2009-2020
PHA7979 Advanced Research
2010-2012,2015-2020,2020
PHA6971 Research for Master’s Thesis
2006,2015-2018,2018-2020
PHA6935 Selected Topics in Pharmacy
2011-2017,2020
PHA6910 Supervised Research
2011,2013-2015,2015-2019,2017-2019,2019
PHA6356 Structure Determination of Complex Natural Products
2015-2018
PHA5439 Prin Med Chem-Pcol I
2016-2018
PHA5782C Patient Care 2
2018
GMS7980 Research for Doctoral Dissertation
2018
CHM7980 Research for Doctoral Dissertation
2018
CHM7979 Advanced Research
2018
MCB7979 Advanced Research
2014-2018
PHA6905C Research Procedures in Medicinal Chemistry
2012-2016
PHA5438 Medicinal Chemistry 2
2015-2016
GMS6009 Principles of Drug Action and Therapeutics
2011-2015
PHA5437 Medicinal Chemistry 1
2012-2015
PHA6934 Seminar in Medicinal Chemistry
2010,2012-2015,2015
PHA6447 Drug Design
2012-2015
PHA5436 Struc/Func Nucleotide
2009,2011
PHA5906 Research in Med Chem

Contact Details

Phones:
Business:
(352) 273-7738
Emails:
Business:
luesch@cop.ufl.edu