Chemical Synthesis and Chaperone Peptide Mediated Folding of Human Nerve Growth Factor by Expressed KAHA Ligation.

ABSTRACT: Nerve growth factor (NGF) is a powerful neurotrophic protein for treating central nervous system diseases, but its therapeutic utility is limited by severe side effects, including hyperalgesia. These adverse effects arise from pleitropic receptor binding that can, in principle, be modulated by side chain mutations or modificationa task suited for chemical protein synthesis. Despite its small size (13 kDa), the chemical synthesis of NGF has been stymied by exceptional hydrophobicity and the requirement for a 104-residue N-terminal "chaperone peptide" for folding. This study presents a chemical synthesis of NGF using α-ketoacid-hydroxylamine (KAHA) ligations, featuring recombinant production of the chaperone peptide and its chemoselective conversion to a C-terminal α-ketoacid. A novel solub

SUBMITTER: Notel NY 

PROVIDER: S-EPMC12395302 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature