Solid-phase synthesis of Stat3 inhibitors incorporating O-carbamoylserine and O-carbamoylthreonine as glutamine mimics

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:17

Article

Mandal, Pijus K. ; Heard, Patricia A. ; Ren, Zhiyong ; Chen, Xiaomin ; McMurray, John S.

关键词: carbamoylserine;    carbamoylthreonine;    Stat3;    signal transducer and activator of transcription 3;    solid-phase peptide synthesis;    rink resin;    phosphopeptide;    peptidomimetic;   

DOI  :  10.1016/j.bmcl.2006.10.099

来源: Elsevier

【 摘 要 】

O-Carbamoyiserine and O-carbamoylthreonine are glutamine analogues that were incorporated into a Stat3 inhibitory peptide to probe the requirements of Gin at the pY+3 position. Fmoc-Ser-NHBn and Fmoc-Thr-NHBn were converted to nitrophenyl carbonates and were attached to Rink resin via a side-chain carbamate linkage. After assembly of the peptide, acid treatment resulted in O-carbamoylserine and O-carbamoylthreonine-containing peptides. The order of affinity for Stat3 was Gin > Ser (CONH2) > Thr(CONH2) suggesting a relatively tight binding pocket for the side chain of glutamine. (c) 2006 Elsevier Ltd. All rights reserved.

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