Synthesis and studies of peptides and analogues involved principally in the renin-angiotensin and kallikrein-kinin system

Abstract

Since we belong to one of the few research groups that not only synthesizes peptides, but has also endeavored to refine this methodology, we have been able to acquire in the last decades, a good level of autonomy in obtaining this relevant class of macromolecules. Peptide analogues have been produced by different strategies, including the use of paramagnetic aminoacids, allowing us good lines of diversification in our research. Based on these considerations, we decided in the present project, to propose a broader line of research and integrated by ten sub-items, weighted principally towards the important physiological systems, renin-angiotensin and kallikrein-kinin. Some peptides present in these systems such as angiotensins, bradykinin and others, together with their analogues containing various alterations, principally of the non-natural type, in their structures, will be examined. The receptors involved in these systems will also be evaluated in different ways, ranging from experiments of site-directed mutations to studies of the difficulties of synthesis, purification and conformational analysis of some of their transmembranar hydrophobic fragments. In addition to classic investigation of the structure-function type, others such as the effect of radiations and of proteolytic enzymes on their structures, as well as the possibility of participation in tumoral processes, will also involve these selected peptides. Complementing these essentially more biological studies, other investigations apparently dissociated from the central theme will also be developed, since all will be inserted, in one way or another, into our continual effort to learn the Chemistry and Physico-Chemistry of peptides. (AU)