Kalman Medzihradszky

A study of the applicability of QSAR calculation for peptide hormones

Abstract A quantitative structure-activity relationship was calculated for the hypothalamic hormone LH-RH. A very good correlation (R > 0.95) and statistically significant equations at 95% confidence limit were obtained using information on the lipophilic nature (π) and steric characteristics (Yγ) of the amino acid side chains.

Antitumor action of N-(2-chloroethyl)-N-nitrosocarbamoyl derivatives of biologically active polypeptide hormone fragments

SummaryThe antitumor action of the 2-chloroethylnitrosocarbamoyl derivatives of peptides related to the 9–13 amino acid residues of α-MSH/ACTH and of the C-terminal tetrapeptide analogue of gastrin have been investigated. Series of 2-chloroethylnitrosoureas attached to amino acids, di-, tri-, tetra-, or pentapeptides were examined in a primary screening system. Among these compounds the Pro-Val-, Lys-Pro-Val-, and Trp-Gly-Lys-Pro-Val-containing 2-chloroethylnitrosocarbamoyl groups were the most effective in the L1210 system. The human melanoma xenograft line was also affected by these agents, while colorectal xenografts were insensitive. A combination of tripeptide-2-chloroethyl-nitrosourea with BCNU induced more than additive growth inhibition of L1210 leukemia.

The use of a steric parameter (Yγ) in QSAR calculations for peptide hormones

Abstract A steric parameter (Y γ ) has been derived for α-amino acids to characterize the steric hindrances near to the α-carbon atom. This easily computable variable is suitable for quantitative structure-activity relationship (QSAR) calculations for peptide hormones. Successful multivariate analyses were performed for oxytocin and angiotensin II analogs with the help of parameters describing the lipophilic and steric properties and the measure of dispersion forces. In the case of position 4 substituted oxytocin analogs, the steric, lipophilic and H-bridge forming properties equally account for the different biological activities of the derivatives. In the case of position 5 substituted angiotensin II analogs, primarily the steric parameters account for the biological activity of the series of derivatives.