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The fragmentation characteristics of native and permethylated oligosaccharides using a matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight tandem mass spectrometer are described. The use of two MALDI matrixes, [alpha]-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB), is shown to control the nature and extent of fragmentation observed in collision-induced dissociation experiments on synthetic oligosaccharides. CHCA promotes the occurrence of glycosidic cleavages, whereas DHB promotes a wide range of fragmentations. These latter fragmentations include glycosidic cleavages, cross-ring cleavages, and the formation of 'internal' cleavage ions, which are derived from elimination of substituents from around the pyranose ring. This extensive fragmentation is shown to facilitate the detailed structural characterization of high-mannose and hybrid-type N-glycans purified from avidin. Importantly, the cross-ring fragments reveal linkage information, unambiguously define antennae substitutions, and differentiate isomeric glycoforms.

Research has been conducted on the vancomycin group's glycopeptide antibiotics. The study of the indole-2-carboxylic acid binding to the antibiotic chlororemomycin carried out in investigating the possibility that this binding would occur with negative cooperativity with respect to the antibiotic dimerization is presented.

Work on the relationship between noncovalent structure and free energy of binding has been extended to incorporate the roles of enthalpy and entropy.

It has been possible to determine the primary structure of a fungal secondary metabolite, chlorofusin, using mass spectrometry, NMR and chiral GC-MS. This metabolite antagonizes the p53/MDM2 interaction.

Surface binding of chloroeremomycin to analogues of resistant bacteria cell wall was shown to be a function of vesicle concentration. Lowering the vesicle concentration resulted in a decline in the binding that is attributed to crowding at the vesicle surface. Separating binding enhancements that are due to simple surface concentration effect resulted in a net enhancement of one to two orders of magnitude for every lipopeptide mole that is bound to the surface.

Resistance to vancomycin has grown in recent years, increasing concerns about future treatment of bacterial infection. There are several new semisynthetic glycopeptides that have useful activity against resistant bacterial strains. LY307599 or biphenylchloreremomycin (BCE) is one such antibiotic, which dimerizes strongly and anchors to membranes. The two locating devices may combine to give improved binding at a cell surface.

The result of the nuclear magnetic resonance spectroscopic studies of the solution structure of the glycopeptide antibiotic ristocetin A's dimer complex done by energy minimization, Nuclear Overhauser effect constraints and molecular dynamics calculation shows that the structure is antisymmetric with two monomeric units' tetrasaccharides differing in their orientation. The asymmetry arises because the tetrasaccharides bind in a parallel, head-to-head alignment. There is a pronounced difference between the ligand affinities of the two units to cell wall peptides and this can be confirmed experimentally.

Dimerization in glycopeptide antibiotics is thermodynamically linked to cell wall analogue binding efficiency. A model explains the influence of dimerization in the physiological action of glycopeptide antibiotics and considers homodimer formation. Conformational change is responsible for the cooperativity between ligand binding homodimerization.

Hydrogen-deuterium exchange methods is employed to measure the association constants and dimerization constant for various dimerizing glycopeptide antibiotics. Structural epitopes influence dimerization. The importance of dimerization in the antibiotic activity is proved with the help of dimerization potential and ligand binding affinity.

A study was done on the dimerization of vancomycin, eremomycin, A82846B, ristocetin-psi and eremomycin-psi using 1H NMR spectroscopy. Results show that the antibiotics all form dimers in aqueous solution in the absence of any peptide ligand. The process of dimerization has a large exothermicity which is accounted by the favorable van der Waals interactions. Furthermore, it was shown to play a significant role in the action of the antibiotics.

The entropy of translational and rotational motions involved in bimolecular association featuring amide-amide hydrogen bond interactions was examined. Results indicated that the loss in freedom of motion prevented the progress of bimolecular association. Large values for the free energy contributions of the amide-amide hydrogen bonds manifested the residual motions affecting the reactivity of the compounds. Further studies utilizing peptide binding interactions characterized the partitioning of free energy contributions and ligand extension processes observed.

The phase transition thermodynamics of organic crystals such as alkanes, alkyl carboxylic acids and 2-methyl ketones were used to determine the entropic cost of rotor restrictions and the enthalpy/entropy interactions involved in translational and rotational motions during crystallization. Enhancement in the endothermicity of the dissociation value resulted in the gradual rise in the translational and rotational entropy loss. Sample studies involving agonist-antagonist mechanisms were evaluated based on the observed entropy variations.