New approaches for G-protein coupled receptor ligands identification

G protein-coupled receptors (GPCRs) represent the class of proteins with the highest impact from social, therapeutic and economic point of view. Today, more than 50% of drug targets are based on GPCRs and the annual worldwide sales exceeds 50 billion dollars. GPCRs are involved in all major diseases areas such as cardiovascular, metabolic, neurodegenerative, psychiatric, cancer and infectious diseases. The classical drug discovery process has relied on screening compounds, which interact favorably with the GPCR of interest followed by further chemical engineering as a mean of improving efficacy and selectivity. On the other hand, several new peptides with potential bioactivity are discovery every year. This review will focus on recent advancement on methods for identification of novel peptides with potential ability to activate GPCRs.

O gene da enzima conversora de angiotensina I influencia as alterações do diabetes / Angiotensin converting enzyme (ACE) gene influences diabetes phenotypes

Estudamos a relação entre fenótipos do diabetes/obesidade com o genótipo da ECA, em humanos e camundongos. Analisamos fenótipos em 1600 indivíduos da população de Vitória (genotipados para o polimorfismo da ECA I/D) e em camundongos com 1 a 3 cópias do gene da ECA, submetidos ou não à dieta rica em gordura ou diabetes. Camundongos com 3 cópias apresentaram menor peso, gordura periepididimal e insulinema, no grupo diabético apresentaram maior mortalidade. A relação fenótipo/genótipo encontrada nos camundongos repetiu-se na população. Estes resultados dão suporte à idéia de que o gene da ECA é um importante fator determinante nos fenótipos relacionados à doenças complexas como a síndrome X. We studied the relationship between obesity/diabetes phenotypes and ACE using a human population (1600 individuals where ACE I/D polymorphism was determined) and engineered ACE mice models (nondiabetic or diabetic under high fat diet or control diet). Presence of D allele was significantly associated with decreased body fat percentage in individuals who were at increases risk of being hyperinsulinemic. Body and periepididymal adipose tissue weight were higher in 1-2 copies mice than 3 copies under high fat diet. Taken together these results provide evidence for a direct role of ACE in obesity phenotypes, which may be important to unravel the complexities of metabolic syndrome...