The solid-state catalytic isotope exchange of hydrogen in alpha-conotoxin G1 by the tritium spillover

Tritium-labeled alpha -conotoxin G1 with a molar radioactivity of 35 Ci/mmo l and full biological activity (according to the binding to nicotinic acety lcholine receptor) was obtained by the high-temperature solid-state catalyt ic Isotope exchange (HSCIE). The tritium distribution in the molecule of a- conotoxin G1 was revealed by H-3 NMR spectroscopy. Tritium was found in all amino acid residues except for the Asn4-Pro5-Ala6 fragment. The data on th e comparative reactivity of C-H bonds, the ab initio quantum-chemical calcu lation of the hydrogen exchange reaction, and the information on the spatia l structures of ol-conotoxin G1 in solution and in crystal state allowed us to establish that the reactivity of H atoms may be increased by their inte raction with the electron donor O and N atoms at the transition state of th e HSCIE reaction. A decrease in the rate of the HSCIE reaction could be cau sed by both a poor spatial accessibility of C-H bonds and a limited mobilit y of the peptide fragment containing these bonds.