02864naa a2200361 a 450000100080000000500110000800800410001902400380006010000220009824501340012026000090025452017840026365000140204765300290206165300310209070000230212170000300214470000170217470000200219170000250221170000220223670000200225870000170227870000180229570000220231370000140233570000200234970000210236970000200239070000170241070000290242777300460245620317002023-03-20       2015    bl uuuu     u00u1 u    #d7 a10.1371/journal.pone.01450712DOI1 aARCANJO, D. D. R.  aA novel vasoactive proline-rich oligopeptide from the skin secretion of the frog Brachycephalus ephippium.h[electronic resource]  c2015  aProline-rich oligopeptides (PROs) are a large family which comprises the bradykinin-potentiating peptides (BPPs). They inhibit the activity of the angiotensin I-converting enzyme (ACE) and have a typical pyroglutamyl (Pyr)/proline-rich structure at the N- and C-terminus, respectively. Furthermore, PROs decrease blood pressure in animals. In the present study, the isolation and biological characterization of a novel vasoactive BPP isolated from the skin secretion of the frog Brachycephalus ephippium is described. This new PRO, termed BPP-Brachy, has the primary structure WPPPKVSP and the amidated form termed BPPBrachyNH2 inhibits efficiently ACE in rat serum. In silico molecular modeling and docking studies suggest that BPP-BrachyNH2 is capable of forming a hydrogen bond network as well as multiple van der Waals interactions with the rat ACE, which blocks the access of the substrate to the C-domain active site. Moreover, in rat thoracic aorta BPP-BrachyNH2 induces potent endothelium-dependent vasodilatation with similar magnitude as captopril. In DAF-FM DA-loaded aortic cross sections examined by confocal microscopy, BPP-BrachyNH2 was found to increase the release of nitric oxide (NO). Moreover, BPP-BrachyNH2 was devoid of toxicity in endothelial and smooth muscle cell cultures. In conclusion, the peptide BPP-BrachyNH2 has a novel sequence being the first BPP isolated from the skin secretion of the Brachycephalidae family. This opens for exploring amphibians as a source of new biomolecules. The BPP-BrachyNH2 is devoid of cytotoxicity and elicits endothelium-dependent vasodilatation mediated by NO. These findings open for the possibility of potential application of these peptides in the treatment of endothelial dysfunction and cardiovascular diseases.  asecretion  aBrachycephalus ephippium  aProline-rich oligopeptides1 aVASCONCELOS, A. G.1 aCOMERMA-STEFFENSEN, S. G.1 aJESUS, J. R.1 aSILVA, L. P. da1 aPIRES JÚNIOR, O. R.1 aCOSTA-NETO, C. M.1 aOLIVEIRA, E. B.1 aMIGLIOLO, L.1 aFRANCO, O. L.1 aRESTINI, C. B. A.1 aPAULO, M.1 aBENDHACK, L. M.1 aBEMQUERER, M. P.1 aOLIVEIRA, A. P.1 aSIMONSEN, U.1 aLEITE, J. R. de S. de A.  tPlos Onegv. 10, dez. 2015. (Open Access)