title: 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.
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-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. Results indicate that the presence of a fold about the central residues of the parent peptide may be important for activity.
authors.affiliation: Chemistry Department, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Boutard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Turcotte
authors.forename: Kim
authors.initials: K
authors.lastname: Beauregard
authors.forename: Christiane
authors.initials: C
authors.lastname: Quiniou
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: William D
authors.initials: WD
authors.lastname: Lubell
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017472:Receptors, Interleukin-1 / Q000737:chemistry*; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000737:chemistry*
chemical_list: C529594:101.10 peptide; D010455:Peptides; D017472:Receptors, Interleukin-1; D047090:beta-Lactams