Abstract
New structural modifications of the marine shell-less mollusk peptide constituent dolastatin 10 (1) have been synthesized, and evaluated against a variety of cancer cell lines and for their ability to inhibit tubulin polymerization. A number of useful structure-activity relationships were uncovered. The most important observation was that the dolaphenine unit of dolastatin 10 could be satisfactorily replaced with a phenethylamine. Peptide 11C, designated auristatin PE, was found to exhibit inhibition of cancer cell growth and tubulin assembly comparable to that of dolastatin 10.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antineoplastic Agents / chemistry*
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Chemical Phenomena
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Chemistry, Physical
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Depsipeptides
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Drug Screening Assays, Antitumor
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Humans
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Leukemia L1210 / pathology
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Molecular Sequence Data
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Oligopeptides / chemical synthesis
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Oligopeptides / chemistry*
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Structure-Activity Relationship
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Tubulin / metabolism
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Tumor Cells, Cultured / drug effects
Substances
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Antineoplastic Agents
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Depsipeptides
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Oligopeptides
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Tubulin
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dolastatin 10