HENDRIK contact LUESCH

Summary

Affiliation: University of Florida
Country: USA

Publications

  1. doi request reprint Total synthesis and molecular target of largazole, a histone deacetylase inhibitor
    Yongcheng Ying
    Department of Chemistry, Duke University, Durham, North Carolina 27708, USA
    J Am Chem Soc 130:8455-9. 2008
  2. doi request reprint Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp
    Kanchan Taori
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Am Chem Soc 130:1806-7. 2008
  3. doi request reprint Kempopeptins A and B, serine protease inhibitors with different selectivity profiles from a marine cyanobacterium, Lyngbya sp
    Kanchan Taori
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 71:1625-9. 2008
  4. pmc Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Org Chem 75:8012-23. 2010
  5. pmc Cultivated sea lettuce is a multiorgan protector from oxidative and inflammatory stress by enhancing the endogenous antioxidant defense system
    Ranjala Ratnayake
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA
    Cancer Prev Res (Phila) 6:989-99. 2013
  6. pmc Discovery and mechanism of natural products as modulators of histone acetylation
    Lilibeth A Salvador
    Department of Medicinal Chemistry, University of Florida, Gainesville, 32610, USA
    Curr Drug Targets 13:1029-47. 2012
  7. pmc Lyngbyoic acid, a "tagged" fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa
    Jason Christopher Kwan
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    Mol Biosyst 7:1205-16. 2011
  8. ncbi request reprint Towards high-throughput characterization of small molecule mechanisms of action
    Hendrik Luesch
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA
    Mol Biosyst 2:609-20. 2006
  9. ncbi request reprint A functional genomics approach to the mode of action of apratoxin A
    Hendrik Luesch
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 2:158-67. 2006
  10. pmc Lyngbyastatins 8-10, elastase inhibitors with cyclic depsipeptide scaffolds isolated from the marine cyanobacterium Lyngbya semiplena
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA
    Mar Drugs 7:528-38. 2009

Research Grants

  1. Chemistry and Biology of Largazoles
    Hendrik Luesch; Fiscal Year: 2009
  2. Chemistry and Biology of Largazoles
    HENDRIK contact LUESCH; Fiscal Year: 2010

Collaborators

Detail Information

Publications39

  1. doi request reprint Total synthesis and molecular target of largazole, a histone deacetylase inhibitor
    Yongcheng Ying
    Department of Chemistry, Duke University, Durham, North Carolina 27708, USA
    J Am Chem Soc 130:8455-9. 2008
    ..In addition, structure-activity relationship (SAR) studies revealed that the thiol group is the pharmacophore of the natural product. Largazole's HDAC inhibitory activity correlates with its antiproliferative activity...
  2. doi request reprint Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp
    Kanchan Taori
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Am Chem Soc 130:1806-7. 2008
  3. doi request reprint Kempopeptins A and B, serine protease inhibitors with different selectivity profiles from a marine cyanobacterium, Lyngbya sp
    Kanchan Taori
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 71:1625-9. 2008
    ..Kempopeptin A (1) exhibited an IC50 against elastase of 0.32 microM and against chymotrypsin of 2.6 microM, while kempopeptin B (2) inhibited trypsin with an IC50 of 8.4 microM...
  4. pmc Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Org Chem 75:8012-23. 2010
    ..Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense...
  5. pmc Cultivated sea lettuce is a multiorgan protector from oxidative and inflammatory stress by enhancing the endogenous antioxidant defense system
    Ranjala Ratnayake
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA
    Cancer Prev Res (Phila) 6:989-99. 2013
    ..Nqo1 activity and NO production were abrogated in nrf2(-/-) mouse embryonic fibroblasts, providing a direct link between the induction of phase II response and anti-inflammatory activity...
  6. pmc Discovery and mechanism of natural products as modulators of histone acetylation
    Lilibeth A Salvador
    Department of Medicinal Chemistry, University of Florida, Gainesville, 32610, USA
    Curr Drug Targets 13:1029-47. 2012
    ..We review the discovery of these compounds and discuss their modes of inhibition together with their downstream biological effects...
  7. pmc Lyngbyoic acid, a "tagged" fatty acid from a marine cyanobacterium, disrupts quorum sensing in Pseudomonas aeruginosa
    Jason Christopher Kwan
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    Mol Biosyst 7:1205-16. 2011
    ..Compound 4 may therefore prove to be a useful tool in the study of P. aeruginosa adaption during such chronic infections...
  8. ncbi request reprint Towards high-throughput characterization of small molecule mechanisms of action
    Hendrik Luesch
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA
    Mol Biosyst 2:609-20. 2006
    ..Current methodologies and technologies are discussed, including how these global approaches complement affinity-based target identification strategies...
  9. ncbi request reprint A functional genomics approach to the mode of action of apratoxin A
    Hendrik Luesch
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Chem Biol 2:158-67. 2006
    ..We conclude that apratoxin A mediates its antiproliferative activity through the induction of G1 cell cycle arrest and an apoptotic cascade, which is at least partially initiated through antagonism of FGF signaling via STAT3...
  10. pmc Lyngbyastatins 8-10, elastase inhibitors with cyclic depsipeptide scaffolds isolated from the marine cyanobacterium Lyngbya semiplena
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA
    Mar Drugs 7:528-38. 2009
    ..Compounds 1-3 are closely related to lyngbyastatins 4-7. Like the latter compounds, we found 1-3 to inhibit porcine pancreatic elastase, with IC(50) values of 123 nM, 210 nM and 120 nM, respectively...
  11. pmc Intramolecular modulation of serine protease inhibitor activity in a marine cyanobacterium with antifeedant properties
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA
    Mar Drugs 8:1803-16. 2010
    ..The cyclization resulted in diminished activity, but to different extents against two serine proteases tested. This finding suggests that cyanobacteria can endogenously modulate the activity of their protease inhibitors...
  12. pmc Tiglicamides A-C, cyclodepsipeptides from the marine cyanobacterium Lyngbya confervoides
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    Phytochemistry 70:2058-63. 2009
    ....
  13. ncbi request reprint Symplostatin 3, a new dolastatin 10 analogue from the marine cyanobacterium Symploca sp. VP452
    Hendrik Luesch
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
    J Nat Prod 65:16-20. 2002
    ..9 to 10.3 nM. It disrupts microtubules, but at a higher concentration than 2, correlating with the weaker in vitro cytotoxicity...
  14. ncbi request reprint New apratoxins of marine cyanobacterial origin from Guam and Palau
    Hendrik Luesch
    Department of Chemistry, University of Hawaii at Manoa, 96822, Honolulu, HI, USA
    Bioorg Med Chem 10:1973-8. 2002
    ..The 16S rRNA genes of the different apratoxin producers have partially been sequenced and compared, and other genetic differences are currently being revealed...
  15. ncbi request reprint Lyngbyastatin 4, a dolastatin 13 analogue with elastase and chymotrypsin inhibitory activity from the marine cyanobacterium Lyngbya confervoides
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 70:124-7. 2007
    ..Lyngbyastatin 4 (1) selectively inhibits elastase and chymotrypsin in vitro over other serine proteases with IC50 values of 0.03 and 0.30 microM, respectively...
  16. ncbi request reprint Lyngbyaloside B, a new glycoside macrolide from a Palauan marine cyanobacterium, Lyngbya sp
    Hendrik Luesch
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USA
    J Nat Prod 65:1945-8. 2002
    ..The relative stereochemistry for the 12 stereocenters is proposed on the basis of proton-proton spin-coupling constants and ROESY data...
  17. ncbi request reprint Ulongamides A-F, new beta-amino acid-containing cyclodepsipeptides from Palauan collections of the marine cyanobacterium Lyngbya sp
    Hendrik Luesch
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
    J Nat Prod 65:996-1000. 2002
    ..All compounds except 6, which lacks an aromatic amino acid moiety, were weakly cytotoxic against KB cells...
  18. pmc Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    J Med Chem 52:5732-47. 2009
    ..We investigated the structural basis of this selectivity using molecular docking. We also show that 1 can reduce antigen presentation by dendritic cells, a process thought to rely on cathepsin E...
  19. doi request reprint Combinatorial strategies by marine cyanobacteria: symplostatin 4, an antimitotic natural dolastatin 10/15 hybrid that synergizes with the coproduced HDAC inhibitor largazole
    Kanchan Taori
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA
    Chembiochem 10:1634-9. 2009
    ..sample that produced the histone deacetylase inhibitor largazole. Both agents in combination are more effective in inhibiting cancer cell proliferation than either agent alone...
  20. ncbi request reprint Lyngbyastatins 5-7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp
    Kanchan Taori
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 70:1593-600. 2007
    ..Compounds 1- 4 were found to selectively inhibit elastase over several other serine proteases, with IC50 values for porcine pancreatic elastase ranging from 3 to 10 nM...
  21. ncbi request reprint Apratoxin a reversibly inhibits the secretory pathway by preventing cotranslational translocation
    Yanxia Liu
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL 32610, USA
    Mol Pharmacol 76:91-104. 2009
    ..Our study indicates that apratoxins are new tools to study the secretory pathway and raises the possibility that inhibition of cotranslational translocation may be exploited for anticancer drug development...
  22. pmc Largamides A-C, tiglic acid-containing cyclodepsipeptides with elastase-inhibitory activity from the marine cyanobacterium Lyngbya confervoides
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    Planta Med 75:528-33. 2009
    ..Compounds 1-3 are moderate inhibitors of mammalian elastase activity in vitro with IC(50) values ranging from 0.53 to 1.41 microM...
  23. ncbi request reprint Total structure determination of grassypeptolide, a new marine cyanobacterial cytotoxin
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    Org Lett 10:789-92. 2008
    ..Grassypeptolide (1) inhibited cancer cell growth with IC50 values from 1.0 to 4.2 microM...
  24. pmc A genomic screen for activators of the antioxidant response element
    Yanxia Liu
    Department of Medicinal Chemistry, University of Florida, 1600 Southwest Archer Road, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 104:5205-10. 2007
    ..This work and other such studies may provide mechanisms for activating the ARE in the absence of general oxidative stress and a yet-unexploited therapeutic approach to degenerative diseases and aging...
  25. doi request reprint Apratoxin E, a cytotoxic peptolide from a guamanian collection of the marine cyanobacterium Lyngbya bouillonii
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, Florida 32610, USA
    J Nat Prod 71:1113-6. 2008
    ..The 5- to 15-fold reduced activity compared with apratoxin A (2) is attributed to the dehydration in the long-chain polyketide unit, which could affect the conformation of the molecule...
  26. doi request reprint Synthesis and activity of largazole analogues with linker and macrocycle modification
    Yongcheng Ying
    Department of Chemistry, Duke University, Durham, North Carolina 27708, USA
    Org Lett 10:4021-4. 2008
    ..However, the valine residue in the macrocycle can be replaced with alanine without significant loss of activity...
  27. pmc Caylobolide B, a macrolactone from symplostatin 1-producing marine cyanobacteria Phormidium spp. from Florida
    Lilibeth A Salvador
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    J Nat Prod 73:1606-9. 2010
    ..Caylobolide B (1) displayed cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells with IC(50) values of 4.5 and 12.2 μM, respectively...
  28. pmc Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor
    Yanxia Liu
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, P O Box 100485, Gainesville, FL 32610, USA
    J Pharmacol Exp Ther 335:351-61. 2010
    ..This effect probably is mediated by the modulation of levels of cell cycle regulators, antagonism of the AKT pathway through insulin receptor substrate 1 down-regulation, and reduction of epidermal growth factor receptor levels...
  29. doi request reprint A natural products approach to drug discovery: probing modes of action of antitumor agents by genome-scale cDNA library screening
    Hendrik Luesch
    Department of Medicinal Chemistry, University of Florida, Gainesville, FL, USA
    Methods Mol Biol 572:261-77. 2009
    ..This fact provides the basis for drug susceptibility screens employing cDNA libraries. The general procedures to optimize and execute those screens and subsequently validate putative screening hits are discussed in detail...
  30. pmc Cytotoxic halogenated macrolides and modified peptides from the apratoxin-producing marine cyanobacterium Lyngbya bouillonii from Guam
    Susan Matthew
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    J Nat Prod 73:1544-52. 2010
    ..bouillonii collections were highly cytotoxic due to the presence of apratoxin A or apratoxin C. Compounds 1-5 showed weak to moderate cytotoxicity to HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells...
  31. ncbi request reprint Biosynthesis of 4-methylproline in cyanobacteria: cloning of nosE and nosF genes and biochemical characterization of the encoded dehydrogenase and reductase activities
    Hendrik Luesch
    Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, USA
    J Org Chem 68:83-91. 2003
    ....
  32. ncbi request reprint A small-molecule inducer of the antioxidant response element
    Wooyoung Hur
    Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA
    Chem Biol 17:537-47. 2010
    ..AI-1 and its biotinylated derivative are useful pharmacological probes for investigating the molecular details of the cellular antioxidant response...
  33. pmc Isolation and biological evaluation of 8-epi-malyngamide C from the Floridian marine cyanobacterium Lyngbya majuscula
    Jason C Kwan
    Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA
    J Nat Prod 73:463-6. 2010
    ..Both 1 and malyngamide C were found to be cytotoxic to HT29 colon cancer cells (IC(50) 15.4 and 5.2 microM, respectively) and to inhibit bacterial quorum sensing in a reporter gene assay...
  34. ncbi request reprint Continuing studies on the cyanobacterium Lyngbya sp.: isolation and structure determination of 15-norlyngbyapeptin A and lyngbyabellin D
    Philip G Williams
    Department of Chemistry, University of Hawaii at Manoa, Honolulu 96822, USA
    J Nat Prod 66:595-8. 2003
    ..Lyngbyabellin D (3) displayed an IC(50) value of 0.1 microM against the KB cell line...
  35. ncbi request reprint A genome-wide overexpression screen in yeast for small-molecule target identification
    Hendrik Luesch
    Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Chem Biol 12:55-63. 2005
    ..Consistent with the suppression screen, inhibitor 1 bound to Pkc1 in yeast cell lysate and inhibited its activity in vitro. These results demonstrate the utility of this approach for the rapid deconvolution of small-molecule targets...
  36. pmc Activation of the antioxidant response element by specific oxidized metabolites of linoleic acid
    Rui Wang
    Department of Medicinal Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, FL, USA
    Prostaglandins Leukot Essent Fatty Acids 81:53-9. 2009
    ..EKODE requires transcription factor NRF2 and PI3-kinase for ARE activity. The results suggest that specific oxidation products of linoleic acid may initiate responses that lessen damage caused by oxidative stress...
  37. ncbi request reprint Genome-wide overexpression screen for activators of antioxidant gene transcription
    Hendrik Luesch
    Department of Medicinal Chemistry, School of Pharmacy, University of Florida, Gainesville, FL, USA
    Methods Mol Biol 477:343-54. 2008
    ..General screening procedure and subsequent hit validation are discussed in detail...
  38. ncbi request reprint The molecular pharmacology of symplostatin 1: a new antimitotic dolastatin 10 analog
    Susan L Mooberry
    Department of Physiology and Medicine, Southwest Foundation for Biomedical Research, San Antonio, TX 78245 0549, USA
    Int J Cancer 104:512-21. 2003
    ..The data indicate that symplostatin 1 has a mechanism of action similar to dolastatin 10...

Research Grants5

  1. Chemistry and Biology of Largazoles
    Hendrik Luesch; Fiscal Year: 2009
    ....
  2. Chemistry and Biology of Largazoles
    HENDRIK contact LUESCH; Fiscal Year: 2010
    ....