Premium
Insertion of multiple α‐amino γ‐lactam (Agl) residues into a peptide sequence by solid‐phase synthesis on synphase lanterns
Author(s) -
Ronga Luisa,
Jamieson Andrew G.,
Beauregard Kim,
Quiniou Christiane,
Chemtob Sylvain,
Lubell William D.
Publication year - 2010
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21288
Subject(s) - chemistry , lactam , peptide , residue (chemistry) , stereochemistry , circular dichroism , solid phase synthesis , peptide synthesis , allosteric regulation , sequence (biology) , combinatorial chemistry , oligopeptide , amino acid , peptide sequence , receptor , biochemistry , gene
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 α‐amino γ‐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 α‐amino γ‐lactams in the same peptide sequence has been accomplished by this effective method for the solid‐supported combinatorial synthesis of lactam‐bridged peptides. Peptides bearing an Agl residue exhibited curve shapes indicative of turn conformations in their circular dichroism spectra. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 183–191, 2010.