Reactivity toward deamidation of asparagine residues in β‐turn structures

Mimetics of β‐turn structures in proteins have been used to calibrate the relative reactivities toward deamidation of asparagine residues in the two central positions of a β‐turn and in a random coil. N‐Acetyl‐Asn‐Gly‐6‐aminocaproic acid, an acyclic analog of a β‐turn mimic undergoes deamidation of the asparaginyl residue through a succinimide intermediate to generate 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 °C) ≈ 3‐fold faster than does the cyclic β‐turn mimic cyclo‐L‐Asn‐Gly‐Aca] with asparagine at position 2 of the β‐turn. The latter compound, in turn, undergoes deamidation ≈ 30‐fold faster than its positional isomer cyclo‐Gly‐Asn‐Aca] with asparagine at position 3 of the β‐turn. Both cyclic peptides assume predominantly β‐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 predominantly random coil structures. The latter isomer undergoes deamidation 2‐fold slower than the former. Thus the order of reactivity toward deamidation is: asparagine in a random coil ≈ 3× asparagine in position 2 of a β‐turn ≈ 30× asparagine in position 3 of a β‐turn.