Qsar studies of side chain modified DI and TRI-peptides in mimicking the Bio-potency of anti-nociceptive action of enkephalin

ABSTRACT

QSAR Studies of smaller chain peptides has been proposed for predicting enkephalin mimic anti-nociceptive activity using a lipophilic parameter partition coefficient. C Log P Program was developed basically based on the fragmentation approach, has been written in Fortran IV. The test compounds, Ile-Val, Phe-Gly, Asn-Cys, Gly-Cys-Val and Ile-Val-Glu were encoded as topological representation of molecular structures using alpha numeric language smiles notation. Log P values obtained for the smaller chain dipeptides and tri-peptides were -0.481 [Ile-Val]; -1.757 [Phe-Gly]; -4,159 [Asn-Cys]; -2.318 [Gly-Cys-Val] and -1.627 [Ile-Val-Glu]. Substitution of glycyl or L-amino acid residues by D-amino acids at appropriate sites of some bioactive peptides may cause a considerable rise in potency. The effect is most dramatic at the Gly-position of enkephalin. Drugs which are to be targeted for the CNS should have log P value of approximately 2. Hence it was concluded that Phe-Gly and Gly-Cys-Val are selected as potential targets for enkephalin like anti-nociceptive activity