Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides

Terrence R. Burke, Zhu Jun Yao, He Zhao, George W.A. Milne, Li Wu, Zhong Yin Zhang, Johannes H. Voigt

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Three new L-amino acid analogues 12, 18 and 25 have been prepared in protected form suitable for incorporation into peptides by solid-phase synthesis using Fmoc protocols. These agents represent nonphosphorus- containing phosphotyrosyl (pTyr) mimetics, which utilize carboxylic groups to provide functionality normally afforded by the pTyr phosphate group. To demonstrate the utility of these analogues, the protein-tyrosine phosphatase- directed peptides Ac-D-A-D-E-X-L-amide (28 - 30) were prepared, where X = pTyr mimetic. In the case where X = 3-carboxy-4-(O-carboxymethyl)-L-tyrosine (8) a K(i) value of 3.6 μM was obtained against PTP1, which equals the Km of the parent pTyr containing peptide. Besides tyrosine phosphatases, these analogues may be useful in a number of contexts, including SH2 domain and phosphotyrosine binding domain systems.

Original languageEnglish (US)
Pages (from-to)9981-9994
Number of pages14
JournalTetrahedron
Volume54
Issue number34
DOIs
StatePublished - Aug 20 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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