CLONING AND PRIMARY STRUCTURE ANALYSIS OF BRADYKININ-POTENTIANTING PEPTIDES PRECURSORS

HAYASHI, M.A.F.(1), MURBACH, A.F.(1), IANZER, D.(1), SILVA, C.A.(1), PIRES, R.S.(2), SILVEIRA, P.F.(1), SARAI, A.(3), BRITTO, L.R.G.(2), PORTARO, F.C.V.(1), DIVE, V.(3), CAMARGO, A.C.M.(1)

The bradykinin-potentiating peptides (BPPs) present in Bothrops jararaca (Bj) venom were the first naturally occurring angiotensin-converting enzyme (ACE) inhibitor described. The study of the structure and activity of these BPPs and analogues were essential for the development of the ACE inhibitors employed in the medicine for the treatment of cardiovascular problems. Five years ago, we have described the cloning and sequence analysis of a cDNA from snake venom gland coding for both BPPs and C-type natriuretic peptide (CNP), both present in a single precursor protein. Northern blot analysis indicated the presence of a homologous mRNA in the Bj CNS, and the respective cDNA was cloned from the snake brain. A 1.7 Kb cDNA clone encoding a 265 amino acids precursor was isolated and seven BPPs and a CNP could be recognized in its deduced amino acid sequence. Surprisingly, although the brain precursor sequence shows a very high similarity to the venom gland one, their sequences are not identical to each other, showing some substitutions and deletions, that determine the expression of different BPPs isoforms in each snake tissue. Evolutionary analyses were performed based on the comparison of the several BPPs precursors isolated till now. Thus, the question that we address in the present study is whether the snake venom BPPs are merely toxins that coincidentally display strong inhibitory action on the mammalian ACE or whether they represent orthologous compounds of endogenous ACE inhibitors or, moreover, of endogenous bioactive molecules which perform physiological functions through either modulation of the ACE activity or by acting toward not yet determined receptors

Supported by FAPESP

CORRESPONDENCE TO:

MIRIAN HAYASHI, Avenida Vital Brasil, 1500, São Paulo, SP, CEP: 05530-900, Brasil, Email: mirianhayashi@hotmail.com