Current Topics in Medicinal Chemistry - Volume 8, Issue 2, 2008

The idea for this special issue of Current Topics in Medicinal Chemistry was generated during a Gordon Research Conference on Carbohydrates that I attended in 2005. Having attended several of these conferences over the past 25 years, I was struck by the growth in our understanding of the chemistry and biology of carbohydrates, and the possibilities that now exist for the application of that understanding to the development Read More

The design of vaccine adjuvants and stand-alone immunotherapeutics has historically been a mix of alchemy and accident partly because of the complex nature of the molecular mechanisms involved in immune system function. The recent discovery of pattern recognition receptors and toll-like receptors (TLRs) in particular on cells of the immune system has shown the important role that stimulation of these cell receptors by Read More

Heparin, an anticoagulant, has been used in many forms to treat various diseases. These forms include soluble heparin and heparin immobilized to supporting matrices by physical adsorption, by covalent chemical methods and by photochemical attachment. These immobilization methods often require the use of spacers or linkers. This review examines and compares various techniques that have been used for the immobilizatio Read More

Interest in the chemistry and biological properties of non-nucleoside N-glycosidic compounds has gathered pace over the past several years; the occurrence of the N-glycoside moiety in glycoproteins and a range of active natural products has prompted the synthesis of a diverse spectrum of related materials with promising potential in medicinal chemistry. Particularly prominent has been the synthesis of novel N-glycosyl amid Read More

To address the medicinal chemist's need for new synthetic methods for the preparation of unnatural carbohydrates, a new de novo method for carbohydrate synthesis has been developed. These routes use a palladium catalyzed glycosylation reaction to stereoselectively control the anomeric center and subsequent diastereoselective post glycosylation to install the remaining sugar stereocenters. The utility of this me Read More

Synthetic advances made possible chemical assembly of complex oligosaccharide fragments of polysaccharide domains on the surface of human pathogenic bacteria. These oligosaccharides may be recognized by antibodies raised against high molecular weight, native, polysaccharides. In addition to their antigenicity, synthetic oligosaccharides can also function as haptens in their protein conjugates that can elicit not only ol Read More

The surfaces of almost all microbes are decorated with remarkable variations of polysaccharides such as Oantigen, capsular polysaccharides (CPS), and exopolysaccharides (EPS) in bacteria, lipoarabinomannans (LAM) in mycobacteria and lipophosphoglycan (LPG) in Leishmania. These polysaccharides play important roles in many biological processes, and they can function as the virulence determinants in the pathogen Read More

Methods to transform carbohydrates are often complex and tedious, both due to the vast array of naturally occurring and synthetically designed scaffolds which may manifest meager to drastic reactivity, dependent upon the transformation sought and the stereogenic site chosen. In order to facilitate and expedite desired synthetic transformation, many researchers are utililizing microwave and ultrasonic irradiation to achieve Read More

Mental illness affects a quarter of the US population. Recently, it has been shown that new, carbohydrate-based drugs hold promise in the treatment of central nervous system (CNS) disorders. A variety of ways in which drugs of this sort may reduce the symptoms of epilepsy, depression and other affective disorders have been proposed, including: targeting the immune system, disrupting glycolysis, acting at di Read More

CHF5074 - A novel NSAID-derived γ-secretase modulator that reduces brain β-amyloid pathology without peripheral toxicity. Some nonsteroidal ant-inflamatory drugs (NSAIDs) have been shown to decrease Aβ42 production, and upon long-term use, may delay or prevent the onset of Alzheimer's disease (AD) in both transgenic mice and humans [1-3]. The mechanism proposed to account for this effect on Aβ42 is allosteric modula Read More