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Biomedical subjects

R Chandrasekaran

Publications and source records attributed to R Chandrasekaran.

At least 73 records · Page 4Linked to original sources

Visualization of an unwound DNA duplex.

Certain dyes and drugs with planar aromatic components can intercalate these into stacks of base pairs and thereby bind tightly to DNA duplexes. Intercalation at one site usually precludes intercalation between the base pairs immediately adjacent. This exclusion implies that two distinct nucleoside conformations are needed in the dinucleoside phosphates which include the intercalation site. The simplest distinction would involve no more than quantitative differences in the (usually anti) conformations at the glycosidic bonds. This could be reinforced by additional, qualitative differences in the furanose ring puckerings (C-2'-endo and C-3'-endo). For the most pronounced difference there could be qualitative differences (syn and anti) in the conformations of the glycosidic bonds as well as in the conformations of the sugar rings. The model discussed here is an example of this most emphatic distinctiveness, as the nucleosides at the 5' ends of the intercalation sites are C-3'-endo and syn and at the 3' ends are C-2'-endo and anti. X-ray diffraction analysis suggests that a completely unwound allomorph of the DNA duplex can persist in oriented fibres when stabilized by certain platinum-containing intercalators. In the untwisting of (usually) right-handed DNA double helices, unwound duplexes are presumably fleeting intermediates.

Animals↗

Left-handed DNA helices.

The synthetic DNA polymerpoly d(GC) . poly d(GC) has been studied by X-ray diffraction of orientated fibres in which it has either the well known (A or B) randed conformations have been observed with poly d(AC) . poly d(GT) and with poly d(As4T) . poly d(As4T), demonstrating that the novel structure is accessible to any DNA segment with an alternating purine-pyrimidine base sequence.

Base Sequence↗

Conformational analysis of cyclo (L-cystine).

Conformational analysis of cyclo(L-cystine) shows that the diketopiperazine ring has to exist only in the boat form. With this geometry, the molecule can adopt two distinct forms differing mainly in the chirality of the disulphide bridge. In both the P- and M-models, corresponding to dihedral angles of nearly +90 degrees and -90 degrees respectively about the S-S- bond, the molecule displays an approximate two-fold symmetry. According to our semi-empirical energy calculations, the minimum energy of the M-model is --9.2 kcal/mol, only 0.3 kcal/mol lower than that of the P-model. Because the difference between the two minima is so small, neither form is clearly superior to the other. However, the number of low energy conformations of the M-model in the allowed conformational space is significantly larger than that of the P-model by a ratio of 3 to 1, and therefore the former is likely to be thermodynamically favoured.

Cystine↗

Conformation of polypeptide chains containing both L- and D-residues. II. Double-helical structures of poly-LD-peptides.

Polypeptides with alternating L- and D-amino acid residues can take up stereo-chemically satisfactory coaxial double-helical structures, both antiparallel and parallel, which are stabilized by systematic interchain NH...O hydrogen bonds. Semiempirical energy calculations over allowed regions of conformational space have yielded the characteristics of these double-helices. There are four possible types of antiparallel double-helices - A3, A4, A5 and A6, with n, the number of LD peptide units per turn, around 2.8, 3.6, 4.5 and 5.5 respectively, while for the parallel double-helices there are two types, P3 and P4, having similar helical parameters as in A3 and A4. The hydrogen-bonding scheme restricts the pitch in all the models to the narrow range of 10.0 to 11.5 A. All these helices have large central cores whose radii increase proportionately with n. In this respect, A3 and A4 are suitable models for the structure of gramicidin A. In terms of their relative energies, antiparallel double-helices are marginally more stable than those with parallel strands. Our results indicate that the energy differences amongst the members in the antiparallel family are not significant and thus provide an explanation for the polymorphism reported for poly (gamma-benzyl-LD-glutamate).

Amino Acids↗

Combined lactose-D-xylose tolerance test in infancy.

A modified combined oral lactose-D-xylose tolerance test done on ten normal infants showed peak levels of blood glucose and D-xylose levels comparable to the peaks obtained when these tests were done separately in the same subjects. The combined test is recommended to evaluate digestive absorptive function in preference to two separate tolerance tests.

Blood Glucose↗

Carbohydrate intolerance in infants with acute diarrhoea and its complications.

Two hundred and seventy-one infants with acute diarrhoea were studied for the presence of carbohydrate malabsorption and 110 infants (40.6%) were found to have carbohydrate intolerance. Malnutrition and severe diarrhoea were found to increase the predisposition to carbohydrate intolerance. The incidence of major complications, protracted diarrhoea and mortality were significantly higher in the carbohydrate intolerant infants as compared to those with carbohydrate tolerance.

Acid-Base Equilibrium↗

Structures for polyinosinic acid and polyguanylic acid.

X-ray-diffraction analysis of oriented, partially crystalline fibres of polyinosinic acid has resulted in a new molecular model. This model consists of four identical polynucleotide chains related to one another by a fourfold rotation axis. The coaxial helices are righthanded (screw symmetry 23(2)) and have an axial translation per residue h=0.341nm and a rotation per residue t=31.3 degrees . Incorporated in the model are standard bond lengths, bond angles and C-2-endo furanose rings. The nucleotide conformation angles, determined by linked-atom least-squares methods, are orthodox and the fit with the X-ray intensities is good. Each hypoxanthine base is linked to two others by hydrogen bonds involving O-6 and N-1. Further stability may arise from intrachain hydrogen bonds between each ribose hydroxyl group and the phosphate oxygen O-3. If guanine were to be substituted for hypoxanthine in an isogeometrical molecular structure, additional hydrogen bonds could be made between every N-2 and N-7.

Guanine Nucleotides↗