Biomedical subjects
Publications and source records attributed to V Kothekar.
Low-angle diffraction studies on lipid droplets from human atherosclerotic lesions showed 3 characteristic reflections at 96 A, 72 A and 36 A. These reflections could best be accounted for by the consideration of a lamellar model containing globular esterified cholesterol micelles (36 A) surrounded by globular micelles (45--46 A) composed of a phospholipid-cholesterol complex.
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.
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The energetics and models of COX-2 complexed with nonsteroidal anti-inflammatory drugs (NSAIDs) having different degrees of selectivity for two isoforms of COX (COX-2 and COX-1) have been studied using computer modelling approach. The models are obtained for complexes of NS398 (NS), a selective COX-2 inhibitor; indoprofen (Ind), a non-selective inhibitor; di-tert-butylbenzofurans (DHDMBFs) with substituents at the 5th position: CONH(CH2)2OMe (BF1), CONH-c-Pr (BF2), 3-methylene-gamma-butyrolactonyl (BF3) and oxicams namely, meloxicam (Mel), piroxicam (Pir) and tenoxicam (Ten). These were optimized using molecular mechanics (MM) and molecular dynamics (MD) techniques. The binding energies and structures were compared with pharmacological parameters and available results with COX-1. In case of NS a larger difference in the binding energies between COX-2 and COX-1 was noticed as compared to that of Ind. It also had stronger interaction with His90 and Tyr355 which is considered important for COX-2 selectivity. There was a difference in the compactness at the channel entrance between COX-2 selective and non-selective ligands. Models with DHDMBFs and oxicams showed a similar correlation. The results were used to design a peptide inhibitor, Tyr-Arg-Cys-Ala-delta Phe-Cys (Pept) which could fit better in the COX-2 cavity. As per our MD simulation results this peptide inhibitor showed both higher activity and COX-2 selectivity.