Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

Kyeong Lee, Shanthaveerappa K. Boovanahalli, Ky Youb Nam, Sang Uk Kang, Mijeoung Lee, Jason Phan, Li Wu, David S. Waugh, Zhong Yin Zhang, Tai No Kyoung, Jun Lee Jung, Terrence R. Burke

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.

Original languageEnglish (US)
Pages (from-to)4037-4042
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number18
DOIs
StatePublished - Sep 15 2005

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Keywords

  • Bioterrorism
  • PTP1B
  • Tripeptides
  • YopH
  • pTyr mimetics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Lee, K., Boovanahalli, S. K., Nam, K. Y., Kang, S. U., Lee, M., Phan, J., Wu, L., Waugh, D. S., Zhang, Z. Y., Kyoung, T. N., Jung, J. L., & Burke, T. R. (2005). Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors. Bioorganic and Medicinal Chemistry Letters, 15(18), 4037-4042. https://doi.org/10.1016/j.bmcl.2005.06.027