Details

Autor(en) / Beteiligte

• Hu, Haitao
• Ransdell, Anthony S.
• Qu, Hongchang
• Durbin, Jim D.
• Valenzuela, Francisco A.
• Hernandez-Buquer, Selene
• Gonciarz, Malgorzata D.

Titel

Probing the Binding Mechanism of Acylated Peptides to Human Serum Albumin

Ist Teil von

• ACS chemical biology, 2023-05, Vol.18 (5), p.1158-1167

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Peptides represent an increasingly important class of pharmaceutical products. During the last decade or so, acylation with fatty acids has demonstrated considerable success in prolonging the circulating half-life of therapeutic peptides by exploiting the ability of fatty acids to reversibly bind to human serum albumin (HSA), thus significantly impacting their pharmacological profiles. Employing methyl-13C-labeled oleic acid or palmitic acid as probe molecules and exploiting HSA mutants designed to probe fatty acid binding, the signals in two-dimensional (2D) nuclear magnetic resonance (NMR) spectra corresponding to high-affinity fatty acid binding sites in HSA were assigned. Subsequently, using a set of selected acylated peptides, competitive displacement experiments by 2D NMR identified a primary fatty acid binding site in HSA utilized in acylated peptide binding. These results represent an important first step toward understanding the structural basis for acylated peptides binding to HSA.