Examination of the active secondary structure of the peptide 101.10, an allosteric modulator of the interleukin-1 receptor, by positional scanning using β-amino γ-lactams

来自 Wiley

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作者：

N Boutard，S Turcotte，K Beauregard，C Quiniou，S Chemtob，WD Lubell

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摘要：

The relationship between the conformation and biological activity of the peptide allosteric modulator of the interleukin-1 receptor 101.10 (D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH2) has been studied using (R)- and (S)-Bgl residues. Twelve Bgl peptides were synthesized using (R)- and (S)-cyclic sulfamidate reagents derived from L- and D-aspartic acid in an optimized Fmoc-compatible protocol for efficient lactam installment onto the supported peptide resin. Examination of these (R)- and (S)-Bgl 101.10 analogs for their potential to inhibit IL-1β-induced thymocyte cell proliferation using a novel fluorescence assay revealed that certain analogs exhibited retained and improved potency relative to the parent peptide 101.10. In light of previous reports that Bgl residues may stabilize type II′β-turn-like conformations in peptides, CD spectroscopy was performed on selected compounds to identify secondary structure necessary for peptide biological activity. Resu

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关键词：

Freidinger lactams &beta -amino -lactam lactam scanning interleukin-1 receptor 101.10 CD peptide mimic -turn conformational analysis solid-phase peptide synthesis