Mirror-image ligand discovery enabled by single-shot fast-flow synthesis of D-proteins.

ABSTRACT: Widespread adoption of mirror-image biological systems presents difficulties in accessing the requisite D-protein substrates. In particular, mirror-image phage display has the potential for high-throughput generation of biologically stable macrocyclic D-peptide binders with potentially unique recognition modes but is hindered by the individualized optimization required for D-protein chemical synthesis. We demonstrate a general mirror-image phage display pipeline that utilizes automated flow peptide synthesis to prepare D-proteins in a single run. With this approach, we prepare and characterize 12 D-proteins - almost one third of all reported D-proteins to date. With access to mirror-image protein targets, we describe the successful discovery of six macrocyclic D-peptide binders: three to t

SUBMITTER: Callahan AJ 

PROVIDER: S-EPMC10901774 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature