ISOLATION AND CHARACTERIZATION OF A NOVEL BRADYKININ POTENTIATING PEPTIDE (BPP) FROM THE SKIN SECRETION OF Phyllomedusa hypochondrialis (DAUDIN,1802).

Pimenta D.C.(1), Conceição, K. (1), Konno, K. (1), Melo, R.L. (1), Antoniazzi, M.M. (2), Jared, C. (2), Sciani, J.M. (3), Conceição, I.M. (3), Prezoto, B.C. (3),  Camargo, A.C.M. (1)

(1) LETA (Laboratório Especial de Toxinologia Aplicada), Center for Applied Toxinology (CAT/CEPID). Instituto Butantan, Avenida Vital Brasil, 1500, São Paulo, SP, 05503-900, Brazil. (2) Departmento de Biologia Celular. Instituto Butantan, Avenida Vital Brasil, 1500, São Paulo, SP, 05503-900, Brazil. (3) Laboratório de Farmacologia.  Instituto Butantan, Avenida Vital Brasil, 1500, São Paulo, SP, 05503-900, Brazil

Bradykinin potentiating peptides (BPPs) from Bothrops jararaca venom were first described in the middle of 1960s and were the first natural inhibitors of the angiotensin-converting enzyme (ACE). BPPs present a classical motif and can be recognized by their typical pyroglutamyl (Pyr) / proline rich sequences presenting, invariably, a proline residue at the C-terminus. In the present study, we describe the isolation and biological characterization of a novel BPP isolated from the skin secretion of the Brazilian tree-frog Phyllomedusa hypochondrialis. This new BPP, named Phypo Xa presents the sequence Pyr-Phe-Arg-Pro-Ser-Tyr-Gln-Ile-Pro-Pro and is able to potentiate Bradykinin activities in vivo and in vitro, as well as efficiently and competitively inhibit ACE. This is the first canonical BPP (i.e. Pyr-Aaan-Gln-Ile-Pro-Pro) to be found not only in the frog skin but also in any other natural source other than the snake venoms.

KEY WORDS: Phyllomedusa hypochondrialis, Bradykinin-Potentiating peptide, mass spectrometry, de novo sequencing, natural peptides, secretion, Bradykinin.

FINANCIAL SUPPORT: CAT/CEPID, FAPESP, CAPES, CNPq.

CORRESPONDENCE TO: Instituto Butantan - Laboratório Especial de Toxinologia Aplicada. Avenida Vital Brazil 1500, São Paulo – SP, 05503-900, Brazil, Phone/fax: + 55 11 3726-1024, e-mail: dcpimenta@butantan.gov.br