Struture activity relationship in GABA receptors / Relación estructura actividad en receptores de GABA

ABSTRACT

Isoguvacine, isonipecotic acid, THIP and muscimol, agonist on GABA-receptors, were studied, looking for a structure-activity relationship. In this way, a conformational analysis was performed with an empirical atom-atom potential calculation method that was proved with success in previous works on biologically active substances. It has been assumed that hydration should eliminate electrostatic interactions and consequently, calculations are performed on molecules without charges. Muscimol, THIP, isoguvacine and isonipecotic acid are rigid structural analogues of GABA. The conformational analysis yield following result. Muscimol show a free rotation but, for different positions of the rotational group. a distance of 4,4 A- between CO and N was obtained. For the other compounds studied, twisted conformation was obtained, with an important population in each case. For these conformations a common pattem to all of them was found adistance of about 4,4 A- betweeb the CO and N groups. This distance is found in partially folded (gauche-trans) conformations of GABA, with a 50% of the whole population. Then, we assumed that partially folded conformations, with a distance between potentially active sites of 4,4 A- may be important for the recognition at the BABA-receptors