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N R Krishna

Publications and source records attributed to N R Krishna.

68 records · Page 4Linked to original sources
PubMed1981

The conformation of angiotensin II. II. The rates of peptide NH exchange with solvent for [Asn1, Val5]angiotensin II, angiotensin III and saralasin.

The amide hydrogen exchange rates in H2O of two angiotensin agonists (angiotensinamide and angiotensin III) and one angiotensin antagonist (saralasin) have been measured at room temperature by the transfer of solvent saturation method. The NH of His6 is observed to exchange more slowly than predicted for all three peptides, suggesting that it is a participant in an intramolecular hydrogen bond. The NH-C alpha H 1H-NMR coupling constants are measured and found to be constant over the pH range of 5.0 to 6.5. The results are compared with those previously obtained for human angiotensin II and interpreted in terms of a dominant three-dimensional structure common to all four molecules. Two models for this structure are evaluated using the observed NH-C alpha H coupling constants and the reported activity of conformationally restrained derivatives.

Angiotensin Amide↗
PubMed1981

Solution conformation of gramicidin S: An intramolecular nuclear Overhauser effect study.

The solution conformation of gramicidin S in deuterated dimethyl sulfoxide was investigated by using the intramolecular nuclear Overhauser effect experiment. Experimental Overhauser enhancements were compared with predicted values for each of the nine most-stable conformations (M1-M9) calculated by Dygert et al. on the basis of energy-minimization procedures [Dygert, M., Gō, N. & Scheraga, H. A. (1975) Macromolecules 8, 750-761]. By using statistical hypothesis testing, the three lowest-energy conformations (M1, M2, and M3) were shown to give the best fit with the experimental data. All other conformations (M4-M9) were found to be inconsistent with the experimental data.

Journal Article↗
PubMed1981

H N.M.R. study of the conformation of [Glu4] oxytocin and its lanthanide complexes in aqueous solution.

At 400 MHz the 1H chemical shifts, peptide NH-C alpha H coupling constants (JN alpha) and peptide hydrogen exchange rates of [Glu4] oxytocin in aqueous solution closely resemble those previously reported for oxytocin under comparable conditions, indicating that both the parent hormone and its analogue have similar conformations in this solvent. The hydrogen exchange data suggest a dynamic equilibrium between conformation(s) in which the peptide NH's of Asn5 and Cys6 are internally hydrogen bonded and conformation(s) in which these hydrogens are bonded to the solvent. [Glu4] oxytocin forms 1:1 complexes with lanthanide metal ions. The diamagnetic La3+ complex exhibits values of JN alpha very similar to those of the metal free hormone analogue, suggesting that coordination of the metal is accompanied by minimal perturbation of the peptide backbone. Specific average proton-metal distances estimated from Gd3+ induced paramagnetic relaxation effects indicate that the metal is probably coordinated to the Glu4 carboxyl group and the sidechain carbonyl of Asn5. Limiting shifts induced by binding of paramagnetic Yb3+ are also reported.

Hydrogen Bonding↗
PubMed1980

Solution conformation of thymopoietin32-36: a proton nuclear magnetic resonance study.

The aqueous solution conformation of Arg-Lys-Asp-Val-Tyr (TP5), corresponding to positions 32-36 of the thymic hormone thymopoietin has been investigated by proton nuclear magnetic resonance (NMR). This pentapeptide fragment retains the biological activity of the parent protein, viz., induction of selective differentiation of T lymphocytes. All the observed NH and CH resonances of TP5 have been assigned, and the solution conformation of this peptide has been investigated by analysis of chemical shift variations with pH, vicinal NH-C alpha H coupling constant data, and amide hydrogen exchange rates. The latter were measured in H2O by using a combination technique consisting of the transfer of solvent saturation and saturation recovery NMR experiments. The data are compatible with the assumption of a highly motile dynamic equilibrium among different conformations for TP5. A comparison of the amide hydrogen exchange rates of the pentapeptide with that of solvated model compounds shows that Val4-NH is significantly shielded from the solvent. In addition, the chemical shift variations with pH suggest that the guanidino-N epsilon H of arginine is associated with one of the carboxylate groups. These observations provide specific boundary conditions for the construction of molecular models of the conformation(s) of TP5 in aqueous solution.

Fourier Analysis↗
PubMed1979

Unipolar mania revisited.

In a more sophisticated replication of an earlier study (Abrams and Taylor 1974), we examined 77 manic patients, of whom 29 had never suffered a depressive illness, and had two or more manic attacks. These unipolar manics were similar to the 48 bipolar manics for a wide variety of clinical, phenomenological, historical, laboratory and demographic variables, generally supporting our earlier findings. However, the present sample showed a striking excess of males among the unipolar manics, as well as an increased morbid risk for unipolar depression in first-degree relatives. Although not readily explainable, these differences suggest that it is premature to equate unipolar mania with classical bipolar illness. Further studies of unipolar mania are in progress.

Adult↗
PubMed1979

Amide hydrogen exchange rates of peptides in H2O solution by 1H nuclear magnetic resonance transfer of solvent saturation method. Conformations of oxytocin and lysine vasopressin in aqueous solution.

The NH exchange rates in aqueous media of oxytocin and 8-lysine vasopressin (LVP) have been measured by using transfer of solvent saturation method. The data are consistent with a "highly motile" dynamic equilibrium between folded and highly solvated conformations. The highly-motility limit applies to the exchange of NH hydrogens of oxytocin and LVP. Folded structures are more prevalent in oxytocin than in LVP. Partial shielding is indicated for peptide hydrogens of Asn5 and perhaps also Cys6 of oxytocin and for Cys6 of LVP. It is tentatively proposed that the folded conformation of oxytocin in aqueous media may contain a parallel beta-structure in the tocinamide ring consisting of two hydrogen bonds: one between the Tyr2 C = O and Asn5 peptide NH as originally proposed for the preferred conformation of oxytocin in dimethyl sulfoxide (D. W. Urry and R. Walter), and the second between he Cys1 C = O and the Cys6 NH. In LVP the hydrogen bond between the Tyr2 C = O and Asn5 peptide NH appears to be absent. The acylic tripeptide sequences (-Pro-X-Gly-NH2) of both hormones appear to be predominantly solvated. The second-order rate constants for acid catalyzed exchange of the primary amide hydrogens of Gln4, Asn5, and Gly9 of oxytocin are consistently greater for the trans NH than for the corresponding cis NH. This observation can be rationalized in terms of mechanisms involving protonation of either the amide oxygen, or the amide nitrogen, but with limited rotation about the C - N bond.

Lypressin↗
PubMed1978

Solution conformation of peptides by the intramolecular nuclear Overhauser effect experiment. Study of valinomycin-K+.

This study demonstrates how the intramolecular nuclear Overhauser effect (NOE) experiment can be employed quantitatively to select from a set of possible conformations for a peptide or a protein the particular conformation (or a group of conformations) most consistent with the data. This procedure is demonstrated on a model depsipeptide system--valinomycin K+ in CDCl3--for which the solution conformation has been inferred by other methods. The NOE enhancements are very sensitive to the conformations assumed by this antibiotic. It is shown that the set of conformations, collectively labeled as A2 (including the X-ray crystallographic structure) gives a very good description of the NOE enhancements. The structure proposed by Bystrov et al. (1977. Eur. J. Biochem. 78:63) for the uncomplexed valinomycin in nonpolar solvents is also consistent with the experimental data on the potassium complex. Using statistical hypothesis testing involving the Hamilton R-factor ratio criterion, all the other models have been rejected as inconsistent with the experimental data. A general formalism is presented for describing the NOE effects in isotropically reorienting molecules. The formalism is not restricted to the extreme narrowing limit of the rotational correlation times and hence applies to both small and large molecules. Some of the factors that can influence the NOE measurements, viz. anisotropic rotational diffusion, conformational averaging, and nuclear spin diffusion, have been considered in this study.

Magnetic Resonance Spectroscopy↗
PubMed1978

Response to lithium carbonate.

We examined the clinical and research records of 29 acutely ill hospitalized patients with affective disorder who received only lithium carbonate during their first week of treatment. Nineteen patients (Group I) could be continued on lithium ion alone, while 10 patients (Group 2) needed additional somatic treatment. Compared with Group 1, Group 2 patients were significantly younger at illness onset, more severely ill on admission, clinically more "colorful" in dress and behavior, stayed more than twice as long in the hospital, and (although not statistically significant) had more than twice the morbidity risk for affective disorder in first-degree relatives. At discharge, both groups were equally improved, and 70% of Group 2 patients were receiving lithium alone. We did not confirm previous reports that nonresponders to lithium alone (Group 2) were more overactive or paranoid--destructive or less euphoric--grandiose than responders to lithium alone (Group 1). Our Group 2 patients had a more severe or penetrant form of illness than our Group 1 patients, requiring neuroleptic drugs or ECT in addition to lithium therapy. Eventually, however, they had a satisfactory outcome, suggesting therapeutic optimism and tenacity even in those patients who initially fail lithium alone and require polytreatment.

Affective Symptoms↗