Computer modelling studies on the modes of binding of some of the α- glycosidically linked disaccharides to concanavalin A.

The possible modes of binding of kojibiose, nigerose, maltose and ManPα(1 →2)Man to concanavalin A have been investigated using computer modelling studies. While α12 linked disaccharides bind to concanavalin A in two modes, i.e. by placing the reducing as well as non-reducing sugar units in the sugar binding site, nigerose or maltose can bind only in one mode, i.e. by placing the non-reducing sugar unit in the binding site. Though, both the sugar residues in α 12 linked disaccharides can reach the binding site, the preference is high for the non-reducing unit. When the non-reducing residue, in any of these disaccharides, enters the binding site, the allowed orientations and the possible hydrogen bonds with the protein seem to be independent of the glycosidic linkage. However, the number of hydrogen bonds the outward sugar residue forms with the protein are dependent on the type of linkage. Atleast one of the hydroxyl groups adjacent to the glycosidic linkage on the outward sugar residue is involved in the formation of a hydrogen bond with the protein suggesting the presence of an extended binding site. The orientation of the reducing sugar residue in the extended binding site is dependent on the linkage. Its orientation in nigerose is flipped when compared to that found in kojibiose or maltose leading to different non-covalent interactions with the protein which affect their binding affinities.

Studies on the conformations of sialyloligosaccharides and implications on the binding specificity of neuraminidases.

Theoretical investigations, using semi-empirical potential functions have been carried out to predict the favoured conformations of the terminal dissaccharide fragments of various sialyloligosaccharides. The proposed conformational similarity for these fragments has been correlated to the binding specificity of neuraminidases. These calculations predict that bacterial neuraminidases have a binding site which can accommodate only two sugar residues and virus neuraminidases have a binding site which can accommodate more than two sugar residues.

Theoretical studies on β-lactam antibiotics VI*: Conformational analysis and structure-activity relationships of penicillin sulfoxides and cephalosporins.

Conformational energy calculations were carried out on penicillin α- and β- sulfoxides and Δ2- and Δ3- cephalosporins, in order to identify the structural features governing their biological activity. Results on penicillin β-sulfoxide indicated that in its favoured conformation, the orientation of the aminoacyl group was different from the one required for biological activity. Penicillin α sulfoxide, like penicillin sulfide, favoured two conformations of nearly equal energies, but separated by a much higher energy barrier. The reduced activity of the sulfoxides despite the nonplanarity of their lactam peptide indicated that the orientations of the aminoacyl and carboxyl groups might also govern biological activity. Δ3- cephalosporins favoured two conformations of nearly equal energies, whereas Δ2- cephalosporins favoured only one conformation. The lactam peptide was moderately nonplanär in the former, but nearly planar in the latter. The differences in the.preferred orientations of the carboxyl group between penicillins and cephalosporins were correlated with the resistance of cephalosporins to penicillinases.

Theoretical studies on β-lactam antibiotics VI*: Conformational analysis and structure-activity relationships of penicillin sulfoxides and cephalosporins.

Conformational energy calculations were carried out on penicillin α- and β- sulfoxides and Δ2- and Δ3- cephalosporins, in order to identify the structural features governing their biological activity. Results on penicillin β-sulfoxide indicated that in its favoured conformation, the orientation of the aminoacyl group was different from the one required for biological activity. Penicillin α sulfoxide, like penicillin sulfide, favoured two conformations of nearly equal energies, but separated by a much higher energy barrier. The reduced activity of the sulfoxides despite the nonplanarity of their lactam peptide indicated that the orientations of the aminoacyl and carboxyl groups might also govern biological activity. Δ3- cephalosporins favoured two conformations of nearly equal energies, whereas Δ2- cephalosporins favoured only one conformation. The lactam peptide was moderately nonplanär in the former, but nearly planar in the latter. The differences in the.preferred orientations of the carboxyl group between penicillins and cephalosporins were correlated with the resistance of cephalosporins to penicillinases.