Biomedical subjects
Publications and source records attributed to A K Bhattacharjee.
Homogeneous murine myeloma immunoglobulins (IgA, kappa), M 384, and M 870, bind methyl alpha-D-galactopyranoside and phosphorylcholine at different subsites. Heterologous recombinant immunoglobulins of these two immunoglobulins with M 603 (a homogeneous IgA, kappa with known phosphorylcholine specificity) also bind phosphorylcholine.
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The application of 13C-nuclear magnetic resonance spectroscopy to the structural determination of the capsular polysaccharide antigens of Neisseria meningitidis is described. Complete assignments of the spectra of the polysaccharides of serogroups A, B, C, W-135, X and Y were made and were based mainly on previous assignments made for the monomer units of the respective polysaccharides. This technique provides information on all structural aspects of the polysaccharides including composition, mode of linkage, location of O-acetyl substituents, sequence, and conformation. In addition, nuclear magnetic resonance is nondestructive, extremely rapid, and has enormous potential in bacteriological research.
The application of gas-liquid chromatography-mass spectrometric (g.l.c.-m.s.) analysis to a number of sialic acid-containing polysaccharides of meningococcal origin has been studied. Methylation of these polysacchardies by the Hakomori conditions resulted in both O- and N-methylation. Methanolysis of the methylated polysaccharides from serogroup C [(2 leads to 9)-linked], colominic acid [(2 leads to 8)-linked], and serogroups Y and W-135 [both (1 leads to 4)-linked], yielded the respective 4,7,8-, 4,7,9-, and 7,8,9-tri-O-methyl derivatives of methyl N-acetyl-N-methyl-beta-D-neuraminate methyl glycoside. As model compounds, methyl N-acetyl-4,7,8,9-tetra-O-methyl-alpha-D-neuraminate methyl glycoside and its N-methyl derivative were also synthesized. All of the methylated derivatives could be identified on the basis of their typical fragmentation-patterns, indicating that this method is applicable to the determination of the position of linkages to sialic acid residues in biopolymers.
The purified high molecular weight serogroup Y meningococcal polysaccharide contains equimolar proportions of D-glucose and N-acetylneuraminic acid and is partially O-acetylated. Carbon-13 nuclear magnetic resonance (NMR) studies, together with other chemical data, have indicated that the polysaccharide is linked only at C-6 of the D-glucose and C-4 of the sialic acid residues, all the linkages being in the alpha-configuration. The 13CNMR data also indicated that the Y polysaccharide is composed of an alternating sequence of these two different residues, and this was confirmed by its autohydrolysis where the major product was 4-O-alpha-D-glucopyranosyl-beta-D-N-acetylneuraminic acid. The W-135 polysaccharide differs from that of Y only in the absence of O-acetylation and in the configuration of one hydroxyl group of the disaccharide repeating unit. In this case autohydrolysis yielded 4-O-alpha-D-galactopyranosyl-beta-D-N-acetylneuraminic acid as the major product. Structural evidence indicates that the BO and Y polysaccharides are identical. Methanolysis of the Y polysaccharide yielded in addition to the methyl glycosides of glucose and sialic acid, a 9-O-acetyl derivative of the latter. This derivative was formed during the re-N-acetylation process and its formation was mainly due to the presence of sodium ions in the original polysaccharide.
The application of 13-C nuclear magnetic resonance to the analysis of some sialic acid-containing meningococcal polysaccharide antigens is described. Complete assignments of the spectra of both the native serogroup B and the de-O-acetylated serogroup C polysaccharides have been made. These assignments were based on the corresponding data for some related monomers (sialic acid and its alpha-and beta-methylglycosides) and on supportive chemical evidence. The data indicate that the serogroup B polysaccharide is a 2 yields 8-alpha-linked homopolymer of sialic acid, identical in structure with colominic acid from Escherichia coli, whereas the de-O-acetylated serogroup C polysaccharide is a 2 yield 9-alpha-linked homopolymer. The native serogroup C polysaccharide is O-acetylated (1.16 mol of O-acetyl per sialic acid residue), all the O-acetyl substituents being located only at C-7 and C-8 of the sialic acid residues, and in addition contains unacetylated residues (24%). The polysaccharide contains di-O-acetylated residues (O-acetyl on C-7 and C-8), and at least one of the possible monoacetylated residues at C-7 or C-8.
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The effect of treatment of purified cholera enterotoxin with acid at pH 2.0 for 1 h followed by neutralization of the acid on the biological activity of the toxin has been studied. It was found that the material loses 85 to 96% of its skin permeability activity and this loss is neither reversed nor increased after 28 days of storage at 5 to 10 C. Other biological properties such as diarrheagenic activity, lipolysis-stimulating activity, and the lethal dose for mice remain unaffected by acid treatment. These observations indicate that the skin permeability activity is more sensitive to relatively minor changes in molecular structure than are the diarrheal, lipolytic, and mouse lethality activities.
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Molecular similarity analysis of stereoelectronic properties between natural insect juvenile hormone (JH), -a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and N, N-diethyl-m-toluamide (DEET) and its analogs reveals similarities that may aid the design of more efficacious insect repellents and give a better insight into the mechanism of repellent action. The study involves quantum chemical calculations using the AM1 semi-empirical computational method enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds, followed by complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic and the DEET compounds. The similarity of stereoelectronic attributes of the amide/ester moiety, the negative electrostatic potential regions beyond the van der Waals surface, and the large distribution of hydrophobic regions in the compounds appear to be the three important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the van der Waals surface is likely to play a crucial role in molecular recognition interaction with the JH receptor from a distance. This also suggests electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor. The insect repellent property of the DEET analogs may thus be attributed to a conflict of complementarity for the JH receptor binding sites.
We have prepared aminoethyl (AE), aminopropyl (AP), and aminopentyl (APT) derivatives of gentiobiose heptaacetate (GH). These spacer compounds (AEGH, APGH, APTGH) have been coupled to succinylated diphtheria toxoid (Suc.DT) to produce conjugate vaccines. These conjugates all bind to the anti-lipid A human monoclonal antibody A6(H4C5) in an ELISA binding assay. Rabbits immunized with the APGH conjugate vaccine in either Freund's complete adjuvant or aluminum hydroxide gel produced antibody levels of 5120 and 3600 ELISA units, respectively, compared to an antibody level of less than 20 ELISA units for the prebleed sera. Sera from mice immunized with either the aminopropyl or the aminopentyl conjugate had antibody levels of 5120 and 2560 ELISA antibody units, respectively. These antibodies neutralized endotoxin in a Limulus lysate neutralization assay. Protection against the local Shwartzman reaction was demonstrated (p less than 0.05) in eight out of nine rabbits immunized with the Suc-DT-APGH conjugate vaccine compared to three out of 10 rabbits immunized with the carrier protein Suc-DT. Passive transfer experiments demonstrated that four out of five rabbits receiving immune serum were protected from Shwartzman reaction compared to one out of five rabbits receiving normal serum (p less than 0.1). These results indicated that epitopes contained in gentiobiose heptaacetate when properly presented as conjugate vaccines were capable of inducing neutralizing antibodies against endotoxin.
Polysaccharides of Cryptococcus neoformans are considered to have a role in the virulence of this encapsulated fungus. The structure has been determined for the most abundant polysaccharide, a glucuronoxylomannan of varying xylose and ester content. The structural complexity of the capsular material increases from serotype D to A to B to C, but even for the simplest capsule (type D), the immunodeterminants seem to occur only on the side chains. The interactions of some of these groups with antibodies is discussed.