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V Kishore

Publications and source records attributed to V Kishore.

At least 19 recordsLinked to original sources
PubMed1991

Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay.

The kinetic properties and substrate specificity of two well-characterized peptidyl prolyl cis-trans isomerases (PPIases), cyclophilin and the FK-506 binding protein (FKBP), have been previously examined [Fischer, G., Bang, H., Berger, E., & Schellenberger, A. (1984) Biochim. Biophys. Acta 791, 87-97; Harrison, R.K., & Stein, R.L. (1990) Biochemistry 29, 1684-1689; Albers, M.W., Walsh, C.T., & Schreiber, S. L. (1990) J. Org. Chem. 55, 4984-4986]. The chymotrypsin-coupled enzymatic assay employed in these studies suffers from two serious shortcomings. Due to the low equilibrium population of the X-cis-Pro-Phe-pNA isomer (the PPIase substrate), in conjunction with the low solubility of p-nitroaniline generated by chymotrypsin hydrolysis, substrate concentrations in the saturating region are not experimentally attainable. Secondly, the uncatalyzed cis-trans isomerization obscures the interpretation of the initial velocity. As a result of these limitations, the steady-state kinetic parameters (Km,Kcat) have not been determined. Here we introduce an improved version of the spectrophotometric assay and report for the first time the Michaelis constants and turnover numbers for both PPIases with established substrates. The improvements in the experimental conditions originate in a medium-induced increase in the equilibrium population of the cis X-Pro conformer and in conducting the assay at 0 degrees C to suppress the uncatalyzed thermal isomerization. In addition, we present a rigorous mathematical model of the spectrophotometric progress curves that accounts for the contributions of the residual background rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Isomerases↗
PubMed1990

Isotope-edited NMR of cyclosporin A bound to cyclophilin: evidence for a trans 9,10 amide bond.

The binding of a 13C-labeled cyclosporin A (CsA) analog to cyclophilin (peptidyl prolyl isomerase) was examined by means of isotope-edited nuclear magnetic resonance (NMR) techniques. A trans 9,10 peptide bond was adopted when CsA was bound to cyclophilin, in contrast to the cis 9,10 peptide bond found in the crystalline and solution conformations of CsA. Furthermore, nuclear Overhauser effects (NOEs) were observed between the zeta 3 and epsilon 3 protons of the methylleucine (MeLeu) residue at position 9 of CsA and tryptophan121 (Trp121) and phenylalanine (Phe) protons of cyclophilin, suggesting that the MeLeu9 residue of CsA interacts with cyclophilin. These results illustrate the power of isotope-edited NMR techniques for rapidly providing useful information about the conformations and active site environment of inhibitors bound to their target enzymes.

Amides↗
PubMed1990

Nutritional copper deficiency does not affect sponge granuloma formation in the rat.

Sponge granuloma formation was compared in copper-deficient and copper-sufficient rats following feeding of respective diets for 20, 40, or 60 d. Body weight, total blood hemoglobin, and activities of ceruloplasmin and Cu, Zn-superoxide dismutase in plasma were monitored to ascertain copper deficiency. Mean granuloma weights (mg +/- SEM) in copper-deficient and copper-sufficient groups of rats, respectively, were as follows: 37 +/- 2 and 38 +/- 2 after 20 d, 22 +/- 2 and 23 +/- 2 after 40 d, and 19 +/- 1 and 21 +/- 1 after 60 d on respective diets. Thus, nutritional copper deficiency did not have an effect on sponge granuloma formation in the rat.

Animals↗
PubMed1990

Effects of copper aspirinate and aspirin on tissue copper, zinc, and iron concentrations following chronic oral treatment in the adjuvant arthritic rat.

Concentrations of copper, zinc, and iron were analyzed and compared in a number of tissues of adjuvant arthritic rats following 22 d of chronic treatment (per os) with either vehicle, aspirin or copper aspirinate, at doses of 100 mg/kg, 200 mg/kg, or 400 mg/kg. Such chronic treatment resulted in a negative balance in copper, zinc, and iron in many tissues. Among the tissues examined, liver and kidney exhibited the greatest changes in metal concentrations; brain and skeletal muscle exhibited the least. Arthritis-induced changes in the concentrations of all three metals in the liver were reversed upon treatment with aspirin. Treatment with copper aspirinate, on the other hand, resulted in an extremely high accumulation of copper in the liver. Arthritis-induced changes in copper, zinc, and iron concentrations in the pancreas and copper concentration in the plasma were generally not reversed upon treatment with either aspirin or copper aspirinate. Among the three metals examined, the degree of change observed as a result of drug treatments was greatest for iron and least for zinc. Finally, it appeared that the effects of aspirin and copper aspirinate on tissue metal concentrations were independent of the antiarthritic effects of these compounds.

Administration, Oral↗
PubMed1989

Effects of adjuvant arthritis on copper, zinc, and iron metabolism in the rat.

In a study on the effects of adjuvant arthritis on copper (Cu), zinc (Zn), and iron (Fe) metabolism in the rat, most significant changes were observed in the liver and pancreas where arthritis caused a large increase in the concentrations of all three metals. Results also indicated that although arthritis-induced changes in metal concentrations were highly correlated to inflammation and occurred in selected tissues only, these changes were not selective for copper.

Animals↗
PubMed1986

Progesterone secretion in the rat in response to an adjuvant arthritis challenge.

This study was undertaken to determine if progesterone is secreted in response to an adjuvant-induced arthritis challenge in the rat. While the arthritic rat paw volume increased 33%, the plasma progesterone concentration increased from 502 pg/ml in the control rats to 1,202 pg/ml in the arthritic animals. A strong positive correlation was found between the degree of edema and the plasma progesterone concentrations. We suggest that progesterone may play an antiinflammatory role in adjuvant arthritis in the rat.

Animals↗
PubMed1977

Anti-inflammatory and antiproteolytic properties of substituted guanidines.

Ten N-(4-propoxyphenyl)-N'-(4-chlorophenethyl)-N"-substituted guanidines were synthesized from the corresponding 1-(4-propoxyphenyl)-3-substituted thiocarbamides and evaluated for anti-inflammatory and antiproteolytic properties. All substituted guanidines (50 mg/kg) provided 1-31% protection against carrageenin-induced edema in rats. Hydrocortisone (10 mg/kg) and oxyphenbutazone (40 mg/kg), used as reference drugs, exhibited greater anti-inflammatory activity. All substituted guanidines (1 mM) possessed antiproteolytic activity. The degree of protection observed by these compounds against trypsin-induced hydrolysis of bovine serum albumin ranged from 12.9 to 52.0% while such a protection with sodium salicylate (1 mM), used as a reference drug, was 52%. In the present study, the antiproteolytic activity possessed by these compounds was found to bear no relationship with their anti-inflammatory property.

Animals↗
PubMed1976

Anti-inflammatory and antiproteolytic properties of 1-(1-naphthylacetyl)-3-substituted carbamides.

Several 1-(1-naphthylacetyl)-3-substituted carbamides were synthesized, characterized, and evaluated for anti-inflammatory and antiproteolytic activity. The protection afforded by most of these carbamides against carrageenan-induced edema in rats at a dose of 100 mg/kg ranged from 4.4 to 50%. Some of these carbamides, which showed higher protection against carrageenan-induced edema, were further evaluated for their antigranulation effect against cotton pellet-induced granuloma formation in rats. All carbamides showed a poor degree of protection against granuloma formation. The antiproteolytic activity of these carbamides, as reflected by their ability to inhibit trypsin-induced hydrolysis of the bovine serum albumin, was of a low order and was unrelated to their anti-inflammatory activity.

Animals↗
PubMed1976

Protection of carrageenin edema and trypsin hydrolysis of bovine serum albumin by naphthylthiosemicarbazides and their cyclized oxadiazoles.

Seven 1-(naphth-1-ylacetyl)-4-substituted thiosemicarbazides were synthesized and cyclized to the corresponding 2-(naphth-1-ylmethyl)-5-arylamino-1,3,4-oxadiazoles. All compounds, with the exception of two slbstituted oxadiazoles, possessed low anti-inflammatory activity. The protection afforded by these compounds against carrageen-in-induced edema ranged from 3 to 43% where cyclization, in general, decreased anti-inflammatory activity. All compounds (1 mM), possessed antiproteolytic activity where in vitro protection of trypsin-induced hydrolysis of bovine serum albumin, in most cases was greater with oxadiazoles.

Animals↗
PubMed1975

Antiinflammatory and antiproteolytic properties of naphthlthiosemicarbazides and cyclized oxadiazoles.

Eight 1-(naphth-1-ylacetyl)-4-substituted thiosemicarbazides and eight 2-(naphth-1-ylmethyl)-5-arylamino-1,3,4-oxadiazoles were synthesized and evaluated for antiinflammatory and antiproteolytic properties. All thiosemicarbazides (100 mg/kg) provided 14-43% protection against carrageenin-induced edema in rats. Cyclization of thiosemicarbazides to oxadiazoles resulted in significant reduction in the antiinflammatory activity. Some of these thiosemicarbazides also possessed low antiinflammatory activity against cotton-pellet-induced granuloma formation and formaldehyde-induced arthritis in rats. Hydrocortisone and oxyphenbutazone, used as reference drugs, exhibited greater antiinflammatory activity. All compounds possessed antiproteolytic activity. The in vitro protection of trypsin-induced hydrolysis of bovine serum albumin, unlike antiinflammatory activity, was greater with oxadiazoles (30-90%) than the precursor thiosemicarbazides (4-50%) at a final concentration of 1 mM.

Animals↗