Girjesh Govil

Fluidity, permeability and antioxidant behaviour of model membranes incorporated with α-tocopherol and vitamin E acetate

Abstract Magnetic resonance studies reveal a marked difference between the binding of α-tocopherol and that of the corresponding acetate (vitamin E acetate) with dipalmitoylphosphatidylcholine (DPPC) vesicles. This is reflected in differences in the phase-transition curves of the DPPC vesicles incorporated with the two compounds, as well as in the 13C relaxation times and line widths. A model for the incorporation of these molecules in lipid bilayers has been suggested. α-Tocopherol binds strongly with the lipids, possibly through a hydrogen bond formation between the hydroxyl group of the former and one of the oxygen atoms of the latter. The possibility of such a hydrogen bond formation is excluded in vitamin E acetate, which binds loosely through the normal hydrophobic interaction. The model for lipid-vitamin interaction explains the in vitro decomposition of H2O2 by α-tocopherol. α-Tocopherol in conjuction with H2O2 can also act as a free-radical scavenger in the lipid phase. The incorporation of α-tocopherol and vitamin E acetate in DPPC vesicles enhances the permeability of lipid bilayers for small molecules such as sodium ascorbate.

Substance P: Structure, Function, and Therapeutics

Extensive efforts since 1931, on the structural determination of the mammalian tachykinin SP by NMR, CD and IR have turned out to be inconclusive. Studies are now being concentrated on the structural properties and characteristics of various NK receptors (NK(1), NK(2) and NK(3)) with the help of genetics, cloning, receptor engineering, mutagenesis and modeling. This knowledge is now being fruitfully used in the development of non-peptide NK(1) receptor antagonists that essentially block the pharmacological effects of SP. It is now being realized that the simultaneous blockade of two or more receptors gives promising results in emesis, depression and pulmonary obstructive diseases. In addition to the synthetic compounds, the discovery of antagonists from natural origin has added a great value to this field. In this review we have made an attempt to present the structural characteristics of SP, its analogs and antagonists, the structural characteristics of the NK receptor, and structure activity relationships that have helped to improve the therapeutic utilities of SP antagonists.

Quantum chemical studies on the conformational structure of nucleic acids III. Calculation of backbone structure by extended Hückel theory

Abstract Extended Huckel theory has been used to calculate the torsional angles (φ′, ω′, ω, φ, ψ) for the sugar phosphate bonds which lead to stable conformations. The predicted conformations are in good agreement with the experimental observations on nucleosides, nucleotides and polynucleotides. It appears that in a double helical structure, the nonbonded and “stacking” interactions provide the stability to the conformational structure of each strand and these strands are then struck together by hydrogen bonds. The unwinding of the double helix, most likely, occurs through internal rotations about O3′-P and/or P-O5′ bonds.

Solution structure of d-GAATTCGAATTC by 2D NMR: A new approach to determination of sugar geometries in DNA segments

A new approach based on the correlated spectroscopy (COSY) in 2D NMR has been described for determination of sugar geometries in oligonucleotides. Under the usual low resolution conditions employed in COSY, the intensities of cross peaks depend on the magnitudes of coupling constants. There are five vicinal coupling constants in a deoxyribose ring which are sensitive to the sugar geometry. The presence, absence and rough comparison of relative intensities of COSY cross peaks arising from such coupling constants enable one to fix the sugar conformation to a fair degree of precision. The methodology has been applied to d‐GAATTCGAATTC. It is observed that ten out of the twelve nucleotide units in this sequence exhibit a rare Ol′‐endo geometry. The EcoRI cleavage sites (between G and A) in the dodecanucleotide show an interesting variation in the conformation with the two sugars attached to the Gs acquiring a geometry between C2′‐endo and C4′‐endo.

Arginine Activates Glycolysis of Goat Epididymal Spermatozoa: An NMR Study

The present study explores the mechanism underlying the action of L-arginine on the metabolic activity of spermatozoa. Goat epididymal spermatozoa were incubated with different concentrations of L-arginine to determine its effect on the utilization of glucose, fructose, and pyruvate. NMR techniques have been applied to elucidate the effect of L-arginine, L-lysine, and L-ornithine on the glycolysis of epididymal goat spermatozoa. Whereas 31P NMR has been used to estimate the change of pH in the presence of different concentrations of L-arginine, 13C NMR has been used to estimate the substrate consumption and lactate production. At optimal concentration of L-arginine, the forward metabolic rates have been found to increase by two to three times over control experiments. Arginine is not consumed in these reactions, but acts as an activator. Longitudinal relaxation time (T1) measurements indicate that the guanidino group of L-arginine plays an active role in binding to cells. The amino acid L-lysine is less effective, and L-ornithine is ineffective.

Molecular orbital studies on the conformation of phospholipids EHT calculations on the polar end

Recently, semiempirical quantum chemical theories have been used extensively, to study the conformational structure of three major classes of biological molecules: polypeptides, nucleic acids and polysaccharides [l] . In view of the limitations imposed by the computers presently available, such calculations have been performed at a submolecular level but nevertheless have been very successful in predicting stable conformations and metastable structures which may be involved in biological processes. The limitations of the earlier calculations based on classical potential functions as opposed to the quantum chemical calculations, are also well recognised. The present studies are part of a research program (taken up jointly with Prof. R.K. Mishra) involving quantum mechanical calculations on the constituents of biological membranes with an aim to gain insight into the structure of the component molecules and the intraand inter-molecular forces responsible for the molecular architecture of membranes. We are aware that a similar study using classical potential functions is in progress in the laboratories of Vanderkooi [ 21. The phospholipids (fig. 1) are a major constituent of biological membranes. There are evidences to indicate that in the membrane structures, the molecular forces which orient the polar head groups are different from those orienting the long hydrocarbon chains. Thus, a convenient way to reduce the computer time is to

Mechanism of Action of l-arginine on the Vitality of Spermatozoa is Primarily Through Increased Biosynthesis of Nitric Oxide

Abstract The ability of sperm to fertilize the egg is primarily dependent on sperm motility and membrane integrity. Nitric oxide (NO) plays a decisive role in regulating multiple functions within the male reproductive system. The aim of the present study is to determine the mechanism by which l-arginine confers a protective action on spermatozoa obtained from the goat epididymis. NO is synthesized from l-arginine by the enzyme nitric oxide-synthase (NOS) present in spermatozoa. A possible participation of NO and NOS in arginine action has been suggested.

Quantum chemical studies on the conformational structure of nucleic acids IV. calculation of backbone structure by CNDO method

Abstract Quantum chemical calculations using the CNDO/2 method, have been carried out to determine the energetically favoured ranges of the torsional angles (φ′, ω′, ω, φ, ψ) which fix the conformational structure of nucleic acid backbone. The two dimensional isoenergy maps have been constructed in the (ω′, ω) and (φ, ψ) hyperspaces. The variation of total energy with respect to φ′ has also been studied. The results show that the non-bonding interactions play a major role in the conformational stability of nucleic acids and polynucleotides. The theoretical predictions show good correspondence with the experimental data (X-ray and 13 C NMR) as well as the other reported theoretical calculations (EHT, PCILO and classical potential functions). The most favoured structure has the conformational angles close to 240, 290, 290, 180 and 60° and these values lead to a helical structure with a pitch of 34 A and about ten nucleotide units per turn of the helix. The proposed models of Watson & Crick, DNA-B and DNA-C lie in high energy regions.

Nuclear magnetic resonance studies in gases

Abstract There are several reasons why nuclear magnetic resonance (NMR) studies in gases are important. At low pressures the interactions in the gas phase are essentially governed by two body collisions. It is therefore possible to study the intermolecular forces between two molecules approaching one another during collision from their influence on the chemical shifts of the nuclei of the molecules under considerations. The experimental measurements allow one to learn how the chemical shift is perturbed because of the presence of other molecules. This knowledge can then be transferred to interpret solvent effects in condensed phases and for detection of any solvent-solute interactions in such systems.

Quantum chemical studies on the conformational structure of nucleic acids I. Extended Hückel calculations on d-ribose phosphate☆

Abstract The extended Mickel theory has been used to predict the stable conformations of d -ribose phosphate. The results have been compared with those obtained from “contact criterion” and from classical potential functions.