Insertion of Multiple α-Amino γ-Lactam (Agl) Residues into a Peptide Sequence by Solid-Phase Synthesis on SynPhase Lanterns

被引：10

作者：

Ronga, Luisa ^{[1
]}

Jamieson, Andrew G. ^{[1
]}

Beauregard, Kim ^{[2
,3
]}

Quiniou, Christiane ^{[2
,3
]}

Chemtob, Sylvain ^{[2
,3
]}

Lubell, William D. ^{[1
]}

机构：

[1] Univ Montreal, Dept Chim, Montreal, PQ H3C 3J7, Canada

[2] Univ Montreal, Hop St Justine, Res Ctr, Dept Pediat, Montreal, PQ H3T 1C5, Canada

[3] Univ Montreal, Hop St Justine, Res Ctr, Dept Pharmacol, Montreal, PQ H3T 1C5, Canada

来源：

BIOPOLYMERS | 2010年 / 94卷 / 02期

基金：

加拿大健康研究院;

关键词：

alpha-amino gamma-lactam (Agl); Freideinger lactam; SynPhase lanterns; interleukin-1 receptor antagonist; beta-turn; 101.10 (rytvela); peptide; amino acid; FREIDINGER LACTAMS; STEREOSELECTIVE-SYNTHESIS; EFFICIENT SYNTHESIS; CONFORMATION; MODULATION; RECEPTOR; ANALOGS; DESIGN;

D O I：

10.1002/bip.21288

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The insertion of lactams into peptide analogs can enhance potency and improve receptor selectivity. The synthesis of lactam-bridged peptide sequences has been accomplished by a solid-phase approach on SynPhase lanterns using cyclic (R)- and (S)-oxathiazinane ester (2) to annulate the amino lactam residue onto the peptide chain. Parallel synthesis of alpha-amino gamma-lactam analogs of the allosteric modulator of IL-1 receptor 101.10 (D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala: rytvela) was performed by split-mix chemistry on the lanterns. In particular, the double insertion of alpha-amino gamma-lactams in the same peptide sequence has been accomplished by this effective method for the solid-supported combinatorial synthesis of lactum-bridged peptides. Peptides bearing an Agl residue exhibited curve shapes indicative of turn conformations

引用

页码：183 / 191

页数：9

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