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

59 Citations (Scopus)

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

Fingerprint

Phosphoric Monoester Hydrolases
Tyrosine
Peptides
Solid-Phase Synthesis Techniques
Phosphotyrosine
Protein Tyrosine Phosphatases
src Homology Domains
Amides
Phosphates
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides. / Burke, Terrence R.; Yao, Zhu Jun; Zhao, He; Milne, George W A; Wu, Li; Zhang, Zhong-Yin; Voigt, Johannes H.

In: Tetrahedron, Vol. 54, No. 34, 20.08.1998, p. 9981-9994.

Research output: Contribution to journalArticle

Burke, Terrence R. ; Yao, Zhu Jun ; Zhao, He ; Milne, George W A ; Wu, Li ; Zhang, Zhong-Yin ; Voigt, Johannes H. / Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides. In: Tetrahedron. 1998 ; Vol. 54, No. 34. pp. 9981-9994.
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