Head-to-Tail Cyclization of α-Conotoxin TxID Leads to Enhanced Stability in Serum

Peptide biomolecules have important bioactivities and hence their use in drug design and development studies has increased in recent years. Conotoxins are natural peptides that obtained from cone snail venoms and have the potential to be used for chronic pain treatment, Parkinson's disease, schizophrenia, obesity and cancer due to their effects on the nervous system. However, their use as medicines has been limited as they can be easily broken down by many proteolytic enzymes in the body. Several modification methods are used to overcome these disadvantages. Cyclization of the peptide backbone is one such method and has been used to stabilize various linear peptides. In this study, the N- and C - termini of alpha -conotoxin TxID with two disulfide bridges were joined using a six amino acid long GGAAGG linker peptide chain to cyclize the peptide backbone and the serum stability of the cyclized peptide was examined. The cyclic TxID peptide remained intact about 50% in human serum after 24 hours.