Enhancing Auxiliary-Mediated Native Chemical Ligation at Challenging Junctions with Pyridine Scaffolds.

ABSTRACT: To expand the scope of native chemical ligation (NCL) beyond reactions at cysteine, ligation auxiliaries are appended to the peptide N-terminus. After the introduction of a pyridine-containing auxiliary, which provided access to challenging junctions (proline or β-branched amino acids), we herein probe the role of the pyridine-ring nitrogen. We observed side reactions leading to preliminary auxiliary loss. We describe a new easy to attach β-mercapto-β-(4-methoxy-2-pyridinyl)-ethyl (MMPyE) auxiliary, which 1) has increased stability; 2) enables NCL at sterically encumbered junctions (e. g., Leu-Val); and 3) allows removal under mildly basic (pH 8.5) conditions was introduced. The synthesis of a 120 aa long peptide containing eight MUC5AC tandem repeats via ligation of two 60mers demonstrate

SUBMITTER: Trunschke S 

PROVIDER: S-EPMC10091703 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature