Reactivity toward deamidation of asparagine residues in beta-turn structures

Mimetics of beta-turn structures in proteins have been used to calibrate th e relative reactivities toward deamidation of asparagine residues in the tw o central positions of a beta-turn and in a random coil. N-Acetyl-Asn-Gly-6 -aminocaproic acid, an acyclic analog of a beta-turn mimic undergoes deamid ation of the asparaginyl residue through a succinimide intermediate to gene rate N-acetyl-Asp-N-Gly-6-aminocaproic acid (6-aminocaproic acid, hereafter Aca) and N-acetyl-L-iso-aspartyl (isoAsp)-Gly-Aca (pH 8.8, 37 degrees C) a pproximate to 3-fold faster than does the cyclic beta-turn mimic cyclo-[L-A sn-Gly-Aca] with asparagine at position 2 of the beta-turn. The latter comp ound, in turn, undergoes deamidation approximate to 30-fold faster than its positional isomer cyclo-[Gly-Asn-Aca] with asparagine at position 3 of the beta-turn. Both cyclic peptides assume predominantly beta-turn structures in solution, as demonstrated by NMR and circular dichroism characterization . The open-chain compound and its isomer N-acetyl-Gly-Asn-Aca assume predom inantly random coil structures. The latter isomer undergoes deamidation 2-f old slower than the former. Thus the order of reactivity toward deamidation is: asparagine in a random coil approximate to 3xasparagine in position 2 of a beta-turn approximate to 30xasparagine in position 3 of a beta-turn.