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Biomedical subjects

A J Hopfinger

Publications and source records attributed to A J Hopfinger.

At least 73 records · Page 4Linked to original sources
PubMed1980

Theoretical study of N-nitrosamines and their presumed proximate carcinogens.

Quantum mechanical calculations in the MINDO/3 and CNDO/2 approximations have been used to study possible mechanisms of action of the carcinogenic N-nitrosamines. Calculated reaction path profiles show that hydroxylation at either the C-H bonds or the amino nitrogen of the nitrosamine may result in the formation of an alpha-hydroxynitrosamine with some interesting structural and stereochemical constraints. Dissociation of the alpha-hydroxynitrosamine, along a concerted pathway or two-step mechanism, releases the alkyldiazohydroxide which subsequently decomposes to the alkylating agents responsible for cancer induction. On the basis of the results obtained for the decomposition of the alkyldiazohydroxide, the alkylation mechanism of N-nitrosamines does not appear to involve carbocation intermediates or diazomethane. The most likely alternative for the alkylation reaction is, then, direct nucleophilic attack (SN2) on the alkyldiazonium ion by basic sites on the DNA molecule.

Alkylation↗
PubMed1976

Conformational analysis of the glycosaminoglycans. II. Bond-angle studies, torsional potential, and steric map for the beta-D-(1leads to 3) linkage.

The geometry of the glycosidic valence-bond angle for both the beta-D-(1linked to4) and beta-D-(1linked to 3) linkages has been investigated by using CNDO and PCILO molecularorbital techniques on model compounds. In each case, the glycosidic valence-bond angle of minimum energy was about 111 degrees, corresponding to the value observed in ether analogs. A secondary energy-minimum was found near 116 degrees, which is the value experimentally observed for saccharides. It was concluded that long-range intra-and/or inter-molecular interactions are responsible for overall preference for the 116 degrees value of the valence-bond angle. The force constants predicted from the shapes of the 116 degrees bond-angle minima gave poor agreement with the experimental values found for ethers and employed in normal coordinate analyses of saccharides. The results did suggest that the beta-D-(1linked to3) bond angle should be 115.6 degrees, which is smaller than the corresponding beta-D-(1linked to4) bond angle. An intrinsic torsional potential-function and general steric map were also determined for the torsion-angle rotations of the beta-D-(1linked to3) linkage.

Binding Sites↗
PubMed1976

Application of SCAP to drug design. 1. Prediction of octanol-water partition coefficients using solvent-dependent conformational analyses.

The solvent-dependent conformational analysis procedure (SCAP) has been used to predict the octanol-water partition coefficients of 20 different compounds with an average absolute error of 9%. SCAP predicts partition coefficients almost as well as the Hansch procedure using pi constants where the absolute error for the 20 compounds is 5%. In addition to estimating partition coefficients, SCAP allows direct calculation of the corresponding solute-solvent interaction free energies. Moreover, binding free energies, based upon hydrophobic and polar interactions, may also be computed. Such free energies are not calculable using other available methods. SCAP also allows solvation free energies to be compared to, or analyzed with, the various intramolecular free energies of the solute molecule as well as all other associated conformational properties.

Energy Transfer↗
PubMed1976

Conformational analysis of a chain reversal in alpha-chymotrypsin.

A complete conformational analysis of the fold (Asp-Lys-Thr-Gly) (residues 35-38), and additional adjacent residues of alpha-chymotrypsin has been performed. A comparison of these findings with those of Lewis et al. (1) is made, and a discussion of the implications of protein-fold models is discussed. This particular residue sequence prefers to bend over maintaining a helical conformation. However, the bend conformation of the tetramer is different from that of the native bend. The native bend conformation is nearly realized when an additional residue of the native primary structure is added to each side of the tetramer. Early and late folding-sequence studies suggests that while the native fold is of low energy, there are fold-points along the primary structure which are more stable. The structural implications of this finding are discussed.

Amino Acid Sequence↗
PubMed1969

Potential energy fields about nitrogen in choline and ethanolamine: biological function at cellular surfaces.

Partial charge distribution on first and second neighbor atoms to nitrogen in choline and ethanolamine have been calculated. Coulombic and steric parameters were then utilized to evaluate the interaction of a negative test charge with the two molecules. Both the position and the magnitude of the maximum of interaction energy in the two systems were significantly different. The results suggest that ethanolamine interacts more strongly with anions than choline does. This is due principally to steric repulsion of the negative charge by the methyl groups in choline.

Amino Alcohols↗