Inhibition of protein synthesis by didemnins: Cell potency and SAR

D. Ahuja, A. Geiger, J. M. Ramanjulu, M. D. Vera, B. SirDeshpande, A. Pfizenmayer, M. Abazeed, D. J. Krosky, D. Beidler, M. M. Joullié, P. L. Toogood*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Synthetic and naturally occurring didemnins are potent and specific inhibitors of protein synthesis in vitro. Structure - activity analysis indicates a requirement for the intact macrocycle; however, the smaller ring size represented by the didemnin analogue, tamandarin A, is equipotent to didemnin B. Replacement of the N,O-dimethyltyrosine by a N-methylphenylalanine or N-methylleucine residue is also well-tolerated. The rank order for inhibition of protein synthesis in vitro appears to be retained in MCF-7 cells, albeit at much higher potency. This increase in potency is explained for the first time by data indicating that MCF-7 cells can accumulate didemnin B up to 2-3 orders of magnitude compared to the growth medium.

Original languageEnglish (US)
Pages (from-to)4212-4218
Number of pages7
JournalJournal of Medicinal Chemistry
Volume43
Issue number22
DOIs
StatePublished - Nov 2 2000

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Ahuja, D., Geiger, A., Ramanjulu, J. M., Vera, M. D., SirDeshpande, B., Pfizenmayer, A., Abazeed, M., Krosky, D. J., Beidler, D., Joullié, M. M., & Toogood, P. L. (2000). Inhibition of protein synthesis by didemnins: Cell potency and SAR. Journal of Medicinal Chemistry, 43(22), 4212-4218. https://doi.org/10.1021/jm000168v