Reactivity toward deamidation of asparagine residues in beta-turn structures.
Mimetics of beta-turn structures in proteins have been used to calibrate the relative reactivities toward deamidation of asparagine residues in the two 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 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 degrees C) approximately 3-fold faster than does the cyclic beta-turn mimic cyclo-[L-Asn-Gly-Aca] with asparagine at position 2 of the beta-turn. The latter compound, in turn, undergoes deamidation approximately 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 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 approximately 3x(asparagine) in position 2 of a beta-turn approximately 30x (asparagine) in position 3 of a beta-turn.
Xie
M
M
Department of Pharmaceutical Chemistry and the Higuchi Biosciences Center, University of Kansas, Lawrence 66047, USA.
Aubé
J
J
Borchardt
R T
RT
Morton
M
M
Topp
E M
EM
Vander Velde
D
D
Schowen
R L
RL
D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D003641:Deamination; D007700:Kinetics; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D010456:Peptides, Cyclic; D001216:Asparagine