Investigation of novel cyclic structure in glycoconjugate using a simple model system.

Bacterial capsular polysaccharide protein conjugates are a major class of vaccines for preventing severe bacterial infections. The conjugation of a polysaccharide to a carrier protein is critical for inducing adaptive immune response in healthy humans. Due to the high molecular mass and extensive structural heterogeneity of the glycoconjugate, the underlying sugar linkages and polypeptide site selectivity of the conjugation reaction are not well characterized and understood.

Staphylococcus aureus capsular polysaccharides: a structural and synthetic perspective.

The S. aureus bacterium is surrounded by capsular polysaccharides. These capsular polysaccharides are important in the pathogenesis of staphylococcal infection.

Synthesis of D-FucNAc-D-ManNAcA Disaccharides Based On the Capsular Polysaccharides Staphylococcus aureus Type 5 and 8.

To gain a better understanding of the conjugation chemistry taking place at the interface of the capsular polysaccharide repeating units, described herein is the synthesis of two disaccharides. These disaccharides correspond to the connection point of the repeating units of capsular polysaccharide S. aureus serotype 5 (CP5) and serotype 8 (CP8).

Synthesis of the Repeating Unit of Capsular Polysaccharide Staphylococcus aureus Type 5 To Study Chemical Activation and Conjugation of Native CP5.

The chemical synthesis of the repeating unit of S. aureus capsular polysaccharide type 5 equipped with capping methyl groups at the points of propagation of the polysaccharide sequence is described. This model compound was designed to study activation of the full length polysaccharide for conjugation to a carrier protein.

A Concise Synthesis of the Repeating Unit of Capsular Polysaccharide Staphylococcus aureus Type 8.

The first synthesis of the repeating unit of S. aureus capsular polysaccharide type 8 is described. The repeating unit is an unusual trisaccharide sequence of three uncommon sugars, all connected via 1,2-cis linkages.

MMP-13 selective isonipecotamide alpha-sulfone hydroxamates.

A series of N-aryl isonipecotamide alpha-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13.

Orally bioavailable dual MMP-1/MMP-14 sparing, MMP-13 selective alpha-sulfone hydroxamates.

A series of phenyl piperidine alpha-sulfone hydroxamate derivatives has been prepared utilizing a combination of solution-phase and resin-bound library technologies to afford compounds that are potent and highly selective for MMP-13, are dual-sparing of MMP-1 and MMP-14 (MT1-MMP) and exhibit oral bioavailability in rats.

Biochemical, cellular, and anti-inflammatory properties of a potent, selective, orally bioavailable benzamide inhibitor of Rho kinase activity.

Rho kinase, is the most widely studied downstream effector of the small Rho GTPase RhoA. Two Rho kinase isoforms have been described and are frequently referred to in the literature as ROCK1 and ROCK2. The RhoA-Rho kinase pathway has been implicated in the recruitment of cellular infiltrates to disease loci in a number of preclinical animal models of inflammatory disease.

A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 1,2-benzothiazepines.

A series of 5-aryl-3,3-dibutyl-7-(dimethylamino)-1,2-benzothiazepin-4-ol 1,1-dioxides were prepared and were found to inhibit the apical sodium co-dependent bile acid transporter (ASBT) for the potential treatment for hyperlipidemia. Several 1,2-benzothiazepines exhibited low nanomolar in vitro activity. The synthesis and initial in vitro potency data is presented for this novel class of compounds.

Solid Phase Synthesis of beta-Peptoids: N-Substituted beta-Aminopropionic Acid Oligomers.

A solid-phase organic synthesis method has been developed for the preparation of N-substituted-beta-aminopropionic acid oligomers or beta-peptoids 1. Treatment of polymer-bound 4-(benzyloxy)benzyl acrylate 2 with primary amines afforded N-substituted beta-alanines 3. Polymer loadings and product conversions were determined by direct cleavage of resin-bound materials and measurement by (1)H NMR with an internal standard.