Cyclization of the Analgesic α-Conotoxin Vc1.1 With a Non-Natural Linker: Effects on Structure, Stability, and Bioactivity.

ABSTRACT: α-Conotoxin Vc1.1 is a disulfide-rich peptide and a promising drug candidate for treating neuropathic and chronic pain. Backbone cyclization was applied to enhance its drug-like properties, resulting in improved serum stability and oral bioavailability. However, this modification also adversely affected its stability and activity in simulated intestinal fluid (SIF). To address these adverse effects, we explored the use of polyethylene glycol (PEG) linkers as substitutes for peptide backbone cyclization linkers. PEG linkers are smaller, more flexible, and more stable than peptide linkers. Furthermore, previous studies have demonstrated that PEG backbone linkers can enhance the activity of conotoxins. In this study, we synthesized four PEG-backboned cyclic Vc1.1 (cVc1.1) analogues with varyi

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12010462 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature