Total synthesis of mambalgin-1/2/3 by two-segment hydrazide-based native chemical ligation.

Mambalgins are a class of 57-residue polypeptide toxins isolated from the venom of the African mamba. They exhibit potent analgesic effects by inhibiting the acid-sensing ion channels. Classified as members of the family of three-finger toxins, mambalgins contain four pairs of disulfide bridges that help to stabilize the three-finger scaffold. Here, we report the chemical synthesis of functional mambalgin-1/2/3 by using one-step two-segment hydrazide-based native chemical ligation. The two-segment ligation approach reported here may enable efficient production of mambalgin toxins. These synthetic mambalgins are useful compounds for development of diagnostic or therapeutic reagents. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.