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

18 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Yersinia
Protein Tyrosine Phosphatases
Amides
Derivatives
Enzymes
5-methylindole

Keywords

  • Bioterrorism
  • PTP1B
  • pTyr mimetics
  • Tripeptides
  • YopH

ASJC Scopus subject areas

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

Cite this

Lee, K., Boovanahalli, S. K., Nam, K. Y., Kang, S. U., Lee, M., Phan, J., ... 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

Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors. / Lee, Kyeong; Boovanahalli, Shanthaveerappa K.; Nam, Ky Youb; Kang, Sang Uk; Lee, Mijeoung; Phan, Jason; Wu, Li; Waugh, David S.; Zhang, Zhong-Yin; Kyoung, Tai No; Jung, Jun Lee; Burke, Terrence R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 18, 15.09.2005, p. 4037-4042.

Research output: Contribution to journalArticle

Lee, K, Boovanahalli, SK, Nam, KY, Kang, SU, Lee, M, Phan, J, Wu, L, Waugh, DS, Zhang, Z-Y, Kyoung, TN, Jung, JL & Burke, TR 2005, 'Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 18, pp. 4037-4042. https://doi.org/10.1016/j.bmcl.2005.06.027
Lee, Kyeong ; Boovanahalli, Shanthaveerappa K. ; Nam, Ky Youb ; Kang, Sang Uk ; Lee, Mijeoung ; Phan, Jason ; Wu, Li ; Waugh, David S. ; Zhang, Zhong-Yin ; Kyoung, Tai No ; Jung, Jun Lee ; Burke, Terrence R. / Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 18. pp. 4037-4042.
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