SYNTHESIS OF PYROGLUTAMYLASPARAGINE AMIDE DIPEPTIDE FRAGMENT OF VASOPRESSIN, AND THE STEREOSELECTIVITY OF ITS MNEMIC EFFECT

Article abstract of DOI:10.1007/BF02219454

Four diastereomers of pGlu-Asn-NH2 were synthesized.They were considered on one hand as a peptide analogue of piracetam, and on the other as an N-terminal fragment of the major metabolite of vasopressin 4, Cyt⁶>AVP(4-9).The influence of these diastereomers on the memory of rats was studied in the passive avoidance conditioned reflex test.It was shown that L-pGlu-L-Asn-NH2 and D-pGlu-D-Asn-NH2 in the same doses facilitate the training of rats; D-pGlu-D-Asn-NH2 is inactive, and L-pGlu-D-Asn-NH2 has amnestic activity.These facts suggest a receptor mechanism for the action of the dipeptide pGlu-Asn-NH2 and are the basis for a hypothesis for the topology of the nootropic receptor binding site.