title: New proline-rich oligopeptides from the venom of African adders: Insights into the hypotensive effect of the venoms.
abstract: BACKGROUND
  The snakes from the Bitis genus are some of the most medically important venomous snakes in sub Saharan Africa, however little is known about the composition and effects of these snake venom peptides. Considering that the victims with Bitis genus snakes have exacerbate hypotension and cardiovascular disorders, we investigated here the presence of angiotensin-converting enzyme modulators on four different species of venoms.
  
  
  METHODS
  The peptide fractions from Bitis gabonica gabonica, Bitis nasicornis, Bitis gabonica rhinoceros and Bitis arietans which showed inhibitory activity on angiotensin-converting enzyme were subjected to mass spectrometry analysis. Eight proline-rich peptides were synthetized and their potencies were evaluated in vitro and in vivo.
  
  
  RESULTS
  The MS analysis resulted in over 150 sequences, out of which 32 are new proline-rich oligopeptides, and eight were selected for syntheses. For some peptides, inhibition assays showed inhibitory potentials of cleavage of angiotensin I ten times greater when compared to bradykinin. In vivo tests showed that all peptides decreased mean arterial pressure, followed by tachycardia in 6 out of 8 of the tests.
  
  
  CONCLUSIONS
  We describe here some new and already known proline-rich peptides, also known as bradykinin-potentiating peptides. Four synthetic peptides indicated a preferential inhibition of angiotensin-converting enzyme C-domain. In vivo studies show that the proline-rich oligopeptides are hypotensive molecules.
  
  
  CONCLUSIONS
  Although proline-rich oligopeptides are known molecules, we present here 32 new sequences that are inhibitors of the angiotensin-converting enzyme and consistent with the symptoms of the victims of Bitis spp, who display severe hypotension.
authors: Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil.
authors: Roberto T
authors: RT
authors: Kodama
authors: Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil.
authors: Daniela
authors: D
authors: Cajado-Carvalho
authors: Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil.
authors: Alexandre K
authors: AK
authors: Kuniyoshi
authors: Special Laboratory of Applied Toxinology/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, SP, Brazil.
authors: Eduardo S
authors: ES
authors: Kitano
authors: Department of Biochemistry, Federal University of São Paulo, São Paulo, Brazil.
authors: Alexandre K
authors: AK
authors: Tashima
authors: Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil.
authors: Barbara F
authors: BF
authors: Barna
authors: Department of Pharmacology, University of São Paulo, São Paulo, Brazil.
authors: Ana Carolina
authors: AC
authors: Takakura
authors: Special Laboratory of Applied Toxinology/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, SP, Brazil.
authors: Solange M T
authors: SM
authors: Serrano
authors: Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil.
authors: Wilmar
authors: W
authors: Dias-Da-Silva
authors: Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil.
authors: Denise V
authors: DV
authors: Tambourgi
authors: Immunochemistry Laboratory, Butantan Institute, São Paulo, SP, Brazil. Electronic address: fernanda.portaro@butantan.gov.br.
authors: Fernanda V
authors: FV
authors: Portaro
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D031541:Fluorescence Resonance Energy Transfer; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000633:toxicity*; D011392:Proline; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology; D053719:Tandem Mass Spectrometry; D014757:Viper Venoms / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D014757:Viper Venoms; D011392:Proline
keywords: Angiotensin-converting enzyme (ACE); Bitis; Bradykinin-potentiating peptide (BPP); Hypotension; Proline-rich oligopeptide (PRO); Venom