From concept to chemistry: integrating protection group strategy and reaction feasibility into non-natural amino acid synthesis planning.

ABSTRACT: Incorporating non-natural amino acids (NNAAs) into peptides enhances therapeutic properties, including binding affinity, metabolic stability, and in vivo half-life time. The pursuit of novel NNAAs for improved peptide designs faces the challenge of effective synthesis of these building blocks as well as the entire peptide itself. Solid-Phase Peptide Synthesis (SPPS) is an essential technology for the automated assembly of peptides with NNAAs, necessitating careful protection for effective coupling of amino acids in the peptide chain. This process requires orthogonal protection of the reactive groups in individual amino acids after synthesizing them, presenting a challenge in bridging in silico peptide design with chemical synthesis. To address this, we have developed a first-

SUBMITTER: Geylan G 

PROVIDER: S-EPMC12415892 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature