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Biomedical subjects

R Rein

Publications and source records attributed to R Rein.

At least 73 records · Page 4Linked to original sources
PubMed1979

Nucleic acid base and carcinogen metabolite specificities during intercalative interactions between DNA and 4-nitroquinoline 1-oxide.

Intercalation of the carcinogen 4-nitroquinoline 1-oxide (4-NQO) or its metabolic intermediate forms, probably precedes the covalent bond formation of the ultimate carcinogenic form with DNA. A 'complete' empirical-potential energy description of the base-sequence and metabolite specificities of the 4-NQO intercalation process is presented in this work. The important force and structural interaction components are depicted via decomposed energy functions. Energy-minimized intercalated complexes are presented and indicate several interesting characteristics. It is clear that the various intercalated quinoline-metabolites do not generally enter into 'strictly' parallel-planar stacked orientations (unlike the structurally rigid ethidium-intercalated complexes). Intercalation is energetically permitted for six of seven quinoline-metabolites (QMS) studied, although, intercalation into to Pyr(3'-5')Pur sequences is preferred over Pur(3'-5'1Pyr sequences. The three quinoline-metabolites that are more energetically favoured to undergo intercalation than the parent form are also known to enter into the greatest amount of covalent interactions with DNA and its constituents. Thus the present work further suggests the existence of a two-step binding mechanism: intercalation followed by covalent reaction.

4-Nitroquinoline-1-oxide↗
PubMed1979

Stereochemical and dynamic aspects of genetic recombination.

The conformational features of three key intermediates in the gene conversion pathway are described. We have found that the dimensions of the trans turned structure involved in crossover are incompatible with normal H-bond formation occurring in opposing strands within the confines of 23 A axially separated double helices. However, if the separation is reduced to 18 A, slight rotation around the axis can give rise to crossover. A mechanism is proposed in which the crossover junction for short sequences migrates by torsional oscillations. This process is rapid enough to permit strand exchange of 100 bases in less than a millisecond. It is shown that the rotational diffusion mechanism becomes rate limiting for the crossover processes involving longer sequences.

Kinetics↗
PubMed1977

Elements of a DNA-polypeptide recognition code: electrostatic potential around the double helix, and a stereospecific model for purine recognition.

A model for stereospecific complex between a polynucleotide double helix and a twisted beta-ribbon type polypeptide is described. The beta ribbon lies in the major groove with alternate side chains pointing toward the interior of the groove. The base-amino acid complementarities are: Arg, G and Asn or Gln, A. It is shown that this complex can: (a) distinguish between G and A in homopolar sequences; (b) the complex is stabilized by approx. 6 Kcal/mole per hydrogen bond per base pair; (c) the required backbone conformation is in the permitted range of Ramachandran plots.

Arginine↗
PubMed1976

Energetics of the deformation of a peptide unit. Semi-empirical molecular orbital and ab initio study of N-methyl acetamide and N-acetyl-L-alanine N-methyl amide.

The problem of non-planarity of peptide unit has been investigated using N-methyl acetamide as a theoretical model. A semi-empirical molecular orbital method: Iterative Extended Hückel Theory viz. IEHT/2 (Adams S. (1974) Doctoral dissertation, State University of New York at Buffalo, U.S.A.) and non-empirical abinitio method with minimal basis set, STO-3G (Hehre, W.J., Stewart, R.F. and Pople, J.A. (1969) J. Chem. Phys. 51, 2657-2664) were used to probe the energetics of the distortion of a planar peptide unit. Distortion of one of the peptide units in a dipeptide, N-acetyl-L-alanine N-methyl amide has also been investigated using abinitio method. The studies amply demonstrate the possibility of the existence of a non-planar peptide unit. Distortion of about 10-15 degrees is predicted to bring about very small loss in energy. The results are substantiated by results from experimental studies.

Acetamides↗
PubMed1976

Responses of the competent and incompetent lower oesophageal sphincter to pentagastrin and abdominal compression.

Responses of the lower oesophageal sphincter (LOS) to pentagastrin, given by continuous intravenous infusion in doses ranging between 0 and 9 mug/kg/h, and to external abdominal compression were measured by infused catheters in healthy subjects and in a group of patients with reflux oesophagitis. In separate experiments, pressures were measured both by sensors stationary within the LOS, and by repeated continuous withdrawals of sensors from stomach to distal oesophagus. In normal subjects, doses of pentagastrin within the physiological range (0.9 mug/kg/h) produced modest but statistically significant increases in LOS pressure. By comparison, sphincteric responses in patients with oesophagitis were small and a dose of 4-5 mug/kg/h was the lowest that produced a significant increase in LOS pressure. During abdominal compression increases in LOS pressure did not significantly exceed increases in intragastric pressure in either patients or normal subjects. This was so at all doses of pentagastrin that were tested. Hence, there was no evidence of synergism between the effects of pentagastrin and abdominal compression upon the LOS. We infer from our findings that gastrin does play a modest role in the physiological regulation of human LOS tone. Relative insensitivity of the incompetent LOS to pentagastrin represents, we believe, sphincteric muscle failure. Our results are not consistent with the hypothesis that LOS incompetence is due to loss or impairment of an adaptive response of the LOS to alterations in intra-abdominal pressure.

Abdomen↗