Diaminodiacid bridge improves enzymatic and in vivo inhibitory activity of peptide CPI-1 against botulinum toxin serotype A

The replacement of the disulfide bridge of CPI-1, a peptide inhibitor of light chain of Botulinum toxin serotype A, with the thioether-containing and biscarba-containing diaminodiacid bridge leads to a significant decrease in the degradation by trypsin and increase in the detoxification activity in vivo, the addition of hydrophobic or positive amino acid at C-terminus of modified peptides further improves the inhibitory activity. (C) 2021 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Replacing the disulfide bridge of CPI-1 with thioether-containing and biscarba-containing diaminodiacid bridge reduces degradation by trypsin and enhances detoxification activity in vivo. Addition of hydrophobic or positive amino acids at the C-terminus of modified peptides further improves inhibitory activity.