摘要:

AbstractAfter establishing experimental conditions to obtain a reliable partition ratio, P', we measured the value of 59 di‐ and tripeptides composed of amino acids having unionizable side chains in a 1‐octanol/pH 7.0 aqueous phosphate buffer system in order to approximate the true partition coefficient. We then formulated an equation correlating the variations of log P' (pH 7) among peptides with free‐energy‐related physicochemical parameters for the side chain substituents and substructures. The log P' value of di‐ and tripeptides is governed by the sum of the hydrophobicity of the peptide backbone and side chains as well as by the steric effect of side chain substituents on the relative solvation of backbone and terminal functional groups. For peptides containing amino acids with polar side chains, the log P' value is higher than that predicted by these effects. The difference is larger as the polar heteroatom in side chains gets closer to the backbone. This may correspond to the “polar proximity factor” for reductions of hydrophilicity observed when polar groups are crowded together. For the side chain of serine and threonine, the difference is even higher than that expected by the polar proximity effect, presumably due to intramolecular hydrogen b

ISSN:0931-8771    

DOI:10.1002/qsar.19890080302

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractThe previously derived z‐scales for the 20 coded amino acids have been extended to cover non‐coded amino acids. In total, 55 amino acids (35 non‐coded) were multivariately characterized by seven TLC variables, three NMR variables and two theoretical variables, resulting in three extended z‐scales (z1′, z2′ and z3′). These scales were validated in QSAR studies on two different series of peptides. They were used to model 40 bradykinin potentiating pentapeptides, and 48 dipeptides with bitter taste. The former series contained 10 peptides with non‐coded amino acids. Thus, the extended z‐scales were validated both for their coded an

ISSN:0931-8771    

DOI:10.1002/qsar.19890080303

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractQuantitative structure‐activity analysis was carried out for in vitro inhibition of rat liver catechol‐O‐methyl‐transferase by a series of 1,5‐substituted‐3,4‐dihydroxybenzenes. Linear regression analysis showed high correlation of inhibitory activity with both empirical electronic substituent parameters and quantum chemical descriptors. The combined effect of both substituents on lowering the pKa values of catechol hydroxyls and the energy of the lowest unoccupied molecular orbital appeared to be the most important determinant of increasing activity. Both substituents seemed to be also directly involved in binding. Hydrophobicity of the substituent at position 1 and the electronic structure of the substituent at position 5 were correlated with activity. A model for binding interactions of inhibitors was postulated on the basis of the QSAR equa

ISSN:0931-8771    

DOI:10.1002/qsar.19890080304

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractThe electron affinity of five new synthetised quaternary 5‐nitroimidazole derivatives was evaluated by means of quantum mechanical CNDO/S calculations and by polarographic measurements. The final aim of these evaluations was to correlate the electron affinity of the products with their previously tested radiosensitizing efficiencies, in order to elucidate the classification of these products as electroaffinic radiosensitizers, in the same way as many other nitroimidazole compounds. Results from both the experimental and theoretical methods give an equally good evaluation of the product electron affinity. An exponential correlation between the LUMO energy values of the neutral molecular structures and the cellular radiosensitizing efficiencies (D.M.F.) of the products was obtained; and this result enables these quaternary 5‐nitroimidazole derivatives to be classified as electroaffinic radiosensitiz

ISSN:0931-8771    

DOI:10.1002/qsar.19890080305

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractMolecular structure is represented as segmented volume elements of 3‐D principal component score spaces of molecules. Clonidine conformations were analysed by principal component analysis (PCA) and their corresponding conformational energies were regressed on segmented PCA score pattern for each conformation. Conformational energy is interpreted as the “activity” of these molecular conformations. The resulting model is able to predict the energy also for other conformationsnotincluded in the calibration. We suggest that segmented atomic score spaces (SASS) can be a valuable tool in quantitative structure‐activity relationship (QSAR)

ISSN:0931-8771    

DOI:10.1002/qsar.19890080306

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

摘要:

AbstractAn index encoding the structural attribute known as flexibility has been devised based upon the chemical graph. The flexibility definition is based upon the role of molecular size, branching, cycles and heteroatom content. The calculation of the index, phi, uses information from the kappa indexes to encode these contributions. The flexibility index is made equal to the product of kappa‐one and kappa‐two, normalized to the number of atoms in the graph. Examples reveal the structure‐activity potential for the

ISSN:0931-8771    

DOI:10.1002/qsar.19890080307

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080308

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY

ISSN:0931-8771    

DOI:10.1002/qsar.19890080301

出版商:WILEY‐VCH Verlag    

年代:1989

数据来源: WILEY