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
✍ Scribed by Nicolas Boutard; Stéphane Turcotte; Kim Beauregard; Christiane Quiniou; Sylvain Chemtob; William D. Lubell
- Book ID
- 105359965
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 264 KB
- Volume
- 17
- Category
- Article
- ISSN
- 1075-2617
- DOI
- 10.1002/psc.1337
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
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‐NH~2~) 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. Results indicate that the presence of a fold about the central residues of the parent peptide may be important for activity. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.