Chemical conversion of aspartyl peptides to isoaspartyl peptides. A method for generating new methyl-accepting substrates for the erythrocyte D-aspartyl/L-isoaspartyl protein methyltransferase.

摘要: Mammalian protein carboxyl methyltransferases have recently been proposed to recognize atypical configurations of aspartic acid and may possibly function in the metabolism covalently altered cellular proteins. Consistent with this proposal, tetrapeptide tetragastrin, containing a single "normal" L-aspartyl residue (L-Trp-L-Met-L-Asp-L-Phe-NH2) was found here not be an vitro substrate for erythrocyte methyltransferase activity. However, chemical treatment tetragastrin by methyl esterification then de-esterification yielded mixture peptide products, major one which could now enzymatically methylated. We show that new species is isomeric beta-aspartyl form (L-iso-tetragastrin; L-Trp-L-Met-L-Asp-L-Phe-NH2), it appears isomerization proceeds via intramolecular succinimide intermediate during procedure. L-iso-Tetragastrin stoichiometrically methylated (up 90% these experiments) Km enzyme 5.0 microM. Similar several other peptides also resulted formation substrates. This general method converting normal aspartyl isoaspartyl application reverse process as well.