Hormone Analogues with Unique Signaling Profiles from Replacement of α-Residue Triads with β/γ Diads.

ABSTRACT: We have applied an underexplored backbone modification strategy to generate new analogues of peptides that activate two clinically important class B1 G protein-coupled receptors (GPCRs). Most peptide modification strategies involve changing side chains or, less commonly, changing the configuration at side chain-bearing carbons (i.e., l residues replaced by d residues). In contrast, backbone modifications alter the number of backbone atoms and the identities of backbone atoms relative to a poly-α-amino acid backbone. Starting from the peptide agonists PTH(1-34) (the first 34 residues of the parathyroid hormone, used clinically as the drug teriparatide) and glucagon-like peptide-1 (7-36) (GLP-1(7-36)), we replaced native α-residue triads with a diad composed of a β-amino acid residue and a γ

SUBMITTER: Gibadullin R 

PROVIDER: S-EPMC10588032 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature