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Several novel, fully synthetic, carbohydrate-based antitumor vaccines are assembled where each construct consists of multiple cancer-related antigens displayed on a single polypeptide backbone. Advances in synthetic methodology have allowed for the incorporation of a complex oligosaccharide terminating in a sialic acid residue as one of the carbohydrate antigens.

The prospects of reaching homogeneous glycopeptides and, in time, glycoproteins through the medium of chemical synthesis have been explored. The goal set forth in scheme 1-a convergent method for the synthesis of bifunctional glycopeptides has been met and the mechanistic rationale set forth in scheme 2 is supported by the identification of the MES-Na thioester as a reaction intermediate.

Rimonabant (SR-141716A) clinical trials demonstrate that antagonism of the CB1 cannabinoid receptor can result in better glucose control as indicated by a reduction in HbA[sub 1c] levels and an improvement in insulin sensitization in treated patients. These effects may be mediated in part through regulation of white adipose tissue lipolysis, the catabolic process whereby triglyceride stores are hydrolyzed to fatty acids and glycerol. In adipose tissue, catecholamine binding to β-adrenergic receptors activates adenylate cyclase through a G[sub s]-coupled mechanism, thereby increasing intracellular cAMP levels. Subsequent activation of protein kinase A by cAMP results in phosphorylation and activation of hormone-sensitive lipase, the rate-limiting enzyme in lipolysis. To explore the effect of cannabinoid modulation of adenlyate cyclase activity, an HTRF (Homogenous Time-Resolved Fluorescence) assay was established to measure the concentration of intracellular cAMP. The CB1 receptor agonist, R(+)-WIN55, 212-2, inhibited forskolin-stimulated cAMP production in CHO cells expressing the CB1 receptor, and SR-141716A blocked this effect in a dose-dependent manner. Consistent with a G[sub i]-coupling mechanism, pertussis toxin attenuated the CB1 receptor agonist-mediated inhibition but not the stimulation of cAMP production. Similar to the in vitro results, CB1 receptor agonist treatment of ob/ob mice acutely inhibited fasting-induced levels of plasma FFAs, an effect that was blocked by SR-141716A administration. Together, these data provide additional evidence that CB1 receptor antagonism regulates adipose tissue lipid metabolism. [ABSTRACT FROM AUTHOR]

As last year marked the tenth anniversary of the cloning of TRPV1, no attenuation has been observed in the intense interest surrounding this ion channel by both academic labs and pharmaceutical companies alike. Patent searches provide an extensive list of novel TRPV1 antagonists generated within the last 7 years, while literature searches reveal a diverse collection of TRPV1 antagonists that have progressed into pre-clinical in vivo profiling and even clinical development. This review serves to summarize the current knowledge of TRPV1 and TRPV1 antagonists as pain therapeutics and to highlight how use of divergent TRPV1 antagonists is helping to further define the physiological and pathological role of TRPV1 and the scope for TRPV1 antagonist therapies.