Antineoplastic agents 337. Synthesis of dolastatin 10 structural modifications

Anticancer Drug Des. 1995 Oct;10(7):529-44.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / chemistry*
  • Chemical Phenomena
  • Chemistry, Physical
  • Depsipeptides
  • Drug Screening Assays, Antitumor
  • Humans
  • Leukemia L1210 / pathology
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Structure-Activity Relationship
  • Tubulin / metabolism
  • Tumor Cells, Cultured / drug effects

Substances

  • Antineoplastic Agents
  • Depsipeptides
  • Oligopeptides
  • Tubulin
  • dolastatin 10