Structural determination of neutral O-linked oligosaccharide alditols by negative ion LC-electrospray-MS<Superscript>n</Superscript>.

Neutral O-linked oligosaccharides released from the salivary mucin MUC5B were separated and detected by negative ion LC-MS and LC-MS(2). The resolution of the chromatography and the information obtained from collision induced dissociation of detected [M - H](-) ions were usually sufficient to identify the sequence of individual oligosaccharides, illustrated by the fact that 50 different oligosaccharides ranging from disaccharides to nonasaccharides could be assigned from the sample. Fragmentation was shown to yield mostly reducing end sequence fragments (Z(i) and Y(i)), enabling primary sequence assignment. Specific fragmentation pathways or patterns were also detected giving specific linkage information. The reducing end core (Gal/GlcNAcbeta1-3GalNAcol or Gal/GlcNAcbeta1-3(GlcNAcbeta1-6)GalNAcol) could be deduced from the pronounced glycosidic C-3 cleavage and A(i) type cleavages of the reducing end GalNAcol, together with the non reducing end fragment from the loss of a single substituted GalNAcol. Substitution patterns on GlcNAc residues were also found, indicative for C-4 substitution ((0,2)A(i) - H(2)O cleavage) and disubstitution of C-3 and C-4 (Z(i)/Z(i) cleavages). This kind of fragmentation can be used for assigning the mode of chain elongation (Galbeta1-3/4GlcNAcbeta1-) and identification of Lewis type antigens like Lewis a/x and Lewis b/y on O-linked oligosaccharides. In essence, negative ion LC-MS(2) was able to generate extensive data for understanding the overall glycosylation pattern of a sample, especially when only a limited amount of material is available.     

Hydroalkoxylation catalyzed by a gold(I) complex encapsulated in a supramolecular host

Gold(I)-phosphine complexes are readily encapsulated by a tetrahedral supramolecular host (Ga(4)L(6)). We have investigated the catalytic activity of the resulting complexes for the intramolecular hydroalkoxylation of allenes. The catalytic activity of Me(3)PAuBr was increased 8-fold by encapsulation, as determined by initial rate kinetics, and we observed up to 67 catalytic turnovers by Me(3)PAu(+) encapsulated in Ga(4)L(6).     

Gln-Gly cleavage: a dominant dissociation site in the fragmentation of protonated peptides

An understanding of the gas-phase dissociation of protonated peptides within the mass spectrometer is essential for automated high-throughput protein identification. In this communication we describe a facile cleavage of the Gln-Gly peptide bond under low-collisional energy conditions. A variety of synthetic peptides have been analysed where key amino acids have been substituted within the sequence PQGPPQQGGR, which is a consensus repeat present in the tryptic peptides of acidic proline-rich protein 1 (PRP-1). The collision-induced dissociation spectra obtained from the PRP-1 tryptic peptides and the synthetic peptides indicate that facile Gln-Gly cleavage occurs when an X-Gln-Gly-Y sequence is present in a peptide, where X is any amino acid and Y any amino acid other than Gly.     

BDD-based heuristics for binary optimization

In this paper we introduce a new method for generating heuristic solutions to binary optimization problems. We develop a technique based on binary decision diagrams. We use these structures to provide an under-approximation to the set of feasible solutions. We show that the proposed algorithm delivers comparable solutions to a state-of-the-art general-purpose optimization solver on randomly generated set covering and set packing problems.     

Nitration of 2-substituted pyrimidine-4,6-diones,structure and reactivity of 5,5-gem-dinitropyrimidine-4,6-diones

Nitration of some 2-substituted pyrimidine-4,6-diones in sulfuric acid was studied, which afforded previously unknown 5,5-gem-dinitropyrimidine-4,6-diones in high yields. The gem-dinitro products were easily attacked by nucleophiles with concomitant formation of gem-dinitroacetyl derivatives, which in turn could be further hydrolyzed to salts of dinitromethane and triureas.     

Preparation of N-alkylated pyridones via selective N-alkylation of 2-alkoxypyridines on solid phase

Regioselective solid-phase synthesis of N-alkylated 2-pyridones has been carried out starting from 2-halopyridines. Variously substituted 2-halopyridines were linked to a Wang resin in quantitative yields to afford 2-alkoxypyridines. The coupled products were then reacted with a variety of alkyl halides, resulting in tandem alkylation and cleavage from the resin to generate N-alkylated pyridones with no detectable traces of O-alkylated products. The scope and limitations of this exceptionally selective reaction have been studied.