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Biomedical subjects

J R Cann

Publications and source records attributed to J R Cann.

At least 19 recordsLinked to original sources
PubMed1979

Circular dichroism study of the solution conformation of luteinizing hormone releasing hormone.

A systematic investigation has been made into the circular dichroic behavior of luteinizing hormone releasing hormone and its peptide fragments and deletion analogues. The results are interpreted to mean that the hormone exists in solution as an ensemble of conformers with different sensitivities to temperature and solvent composition. The far-ultraviolet circular dichroic spectra exhibited by the hormone under different experimental conditions can be simulated satisfactorily by the weighted addition of the spectra of its aliphatic- and aromatic-containing halves. However, the structure of the hormone is not simply the sum of its halves, since some conformational feature of the intact molecule perturbs the near-ultraviolet circular dichroism of its aromatic residues.

Amino Acid Sequence↗
PubMed1979

Effect of temperature upon the circular dichroism of bradykinin.

Analysis of the effect of temperature on the circular dichroism spectrum of bradykinin has led to a more precise understanding of the solution conformation of the peptide. Circular dichroism and 13C n.m.r. have been used in a complementary fashion to support the picture that bradykinin spends a maximum of about 20% of its time in a partially ordered conformation featuring a gamma-turn with Pro7 as the second residue. Since the gamma-turn probability is insensitive to temperature, some other conformational effect dominated by the structure of water presumably produces the pronounced change in the circular dichroism spectrum with increasing temperature.

Bradykinin↗
PubMed1978

A circular dichroism study of the interaction of chlorpromazine with mouse brain tubulin.

A circular dichroism study with subsidiary ultracentrifuge measurements on the interaction of chlorpromazine with mouse brain tubulin establishes the previous inference from binding studies that the drug induces a change in the structure of the protein. Binding of the first mole of chlorpromazine causes an alteration in secondary structure, which is reversible with respect to drug concentration, without detected change in tertiary structure or significant change in the state of association of the protein. The conformationally altered tubulin binds additional chlorpromazine molecules without further change in secondary structure.

Animals↗
PubMed1978

13C nuclear magnetic resonance study of the cis-trans isomerism in X-Pro-Pro tripeptides.

13C nuclear magnetic resonance has been used to characterize quantitatively the cis-trans isomerism about both peptide bonds in the tripeptides Ser-Pro-Pro and Arg-Pro-Pro. Detailed pH titration data indicate that the configuration about both peptide bonds is closely linked to titration of the terminal carboxyl group and, to a lesser extent, to titration of the terminal amino group. The Pro2 C-3 resonance has been found particularly useful for interpretation due to its sensitivity to the isomerization about both peptide bonds. Analysis of the probabilities of the trans-trans, cic-cis, cis-trans, and trans-cis isomers in aqueous solution indicates a stability decrease in the order given. Similarities in the isomerization behavior of the two peptides indicate that side chain interactions involving the first residue have very little effect on the observed cis/trans ratios. The sensitivity of the cis/trans ratio to titration of the terminal amino group is most readily explained on the basis of an indirect effect on carbonyl-carbonyl repulsion.

Arginine↗
PubMed1978

Isoelectric focusing of a dimerizing solute in rapid chemical equilibrium: comparison of simulation procedures.

The approach to isoelectric focusing equilibrium of a rapidly dimerizing solute was simulated by two different computing procedures: a stationary-grid model developed by Cann and Stimpson and a distorted-grid technique derived from the method of Cox. The results given by the two models were virtually identical at all times during the approach to equilibrium. Of the two procedures, the distorted-grid method has an advantage in computing time, while the stationary-grid model is applicable to a broader range of transport experiments. The effect on the focusing experiment of varying the electric field was examined by distorted-grid simulations. When the field was increased, the equilibrium distribution sharpened somewhat and the peak of the concentration profile shifted toward the isoelectric position of the dimer. The rate of approach to equilibrium was approximately proportional to the field strength.

Isoelectric Focusing↗
PubMed1977

Isoelectric focusing of interacting systems. I. Carrier ampholyte-induced macromolecular isomerization.

A phenomenological theory of isoelectric focusing is formulated for rapidly reversible, ampholyte-induced macromolecular isomerization. The calculations reveal that such interactions can give well resolved, bimodal transient and equilibrium isoelectric focusing patterns in which the two peaks correspond to different chemical equilibrium compositions and not to separated isomers. The kinetics of approach to the equilibrium pattern are characteristically biphasic: During the first phase, which is controlled by the rate of migration of the isomers in the electric field, two peaks are positioned in the region between the isoelectric points of the two isomers; one of the peaks then grows slowly at the expense of the other with a diffusion-dominated rate. The kinetics are dependent upon the initial distribution of macromolecule in the isoelectric focusing column, and in certain cases only a single peak is apparent during the first phase. These findings have practical implications for unambiguous interpretation of isoelectric focusing patterns, furnish explanations for hitherto puzzling experimental observations, and provide theoretical insights required for application of isoelectric focusing to the detection and characterization of macromolecular interactions in general.

Diffusion↗
PubMed1977

Isoelectric focusing of interacting systems. II. pH-dependent conformational transitions.

Transient and equilibrium isoelectric focusing patterns have been computed for pH-dependent conformational transitions in the limits of complete cooperativity and instantaneous chemical equilibration. Transitions induced by the binding of a relatively large number of hydrogen ions by the macromolecule give well resolved bimodal equilibrium patterns, provided that the resulting conformer has the lower isoelectric point. The corresponding transient patterns may be either bimodal or virtually unimodal for practical times of operation depending upon the point of insertion of the sample into the pH gradient and the stoichiometry of the interaction. A macromolecule undergoing sequential transitions can give multimodal isoelectric focussing patterns.

Electricity↗
PubMed1976

Hummel-Dreyer gel chromatographic procedure as applied to ligand-mediated association.

A mass transport theory of the gel chromatographic procedure of Hummel and Dreyer for measuring the binding of small ligand molecules to macromolecules has been formulated for ligand-mediated macromolecular association. It is concluded that the Hummel-Dreyer procedure is the method of choice for quantitating ligand binding in such systems. Guidelines are drawn for unambiguous interpretation of the nonclasical elution profiles in terms of the number of binding sites on the macromonomer and their intrinsic binding constant. Most of these guidelines also apply to static equilibrium methods such as equilibrium dialysis.

Binding Sites↗
PubMed1976

On the solution conformation of bradykinin and certain fragments.

A circular dichroism (CD) study of [D-Pro2]- and [D-Pro3]-bradykinin, selected peptide fragments, and the model compound. N-acetyl-L-phenylalaninamide, support our previous conclusion (Biochemistry 12, 3780, 1973) that the positive 221-nm CD band of bradykinin is a composite of bands due to two chromophores, the 217-nm band characteristic of the Phe residues overlying the 223-nm band of the N-terminal sequence, Arg-Pro-Pro. The results also indicate that the 223-nm band of Arg-Pro-Pro is associated with the configuration of the Pro-Pro sequence, Arg-D-Pro-Pro and Arg-Pro-D-Pro virtually being diastereoisomers. Accordingly, the conformation of Arg-Pro-Pro was probed in further detail. Upon increasing the temperature from about 27 to 65 degrees C, Arg-Pro-Pro undergoes a conformational transition characterized by large positive values of deltaHdegrees and deltaSdegrees, which is interpreted to mean that the structure of water and, thus, solute-solvent interactions play a dominant role in determining the conformation of the peptide 13C nuclear magnetic resonance spectroscopy indicates that the effect of lowering the pH on the CD of Arg-Pro-Pro is explicable in terms of hydrogen-bond formation between the carboxyl group and Pro2 carbonyl oxygen at acid pH with concomitant cis to trans isomerization.

Amino Acids↗