Identification of novel bradykinin-potentiating peptides (BPPs) in the venom gland of a rattlesnake allowed the evaluation of the structure-function relationship of BPPs.
Aiming to extend the knowledge about the diversity of bradykinin-potentiating peptides (BPPs) and their precursor proteins, a venom gland cDNA library from the South American rattlesnake (Crotalus dursissus terrificus, Cdt) was screened. Two novel homologous cDNAs encoding the BPPs precursor protein were cloned. Their sequence contain only one single longer BPP sequence with the typical IPP-tripeptide, and two short potential BPP-like molecules, revealing a unique structural organization. Several peptide sequences structurally similar to the BPPs identified in the precursor protein from Cdt and also from others snakes, were chemically synthesized and were bioassayed both in vitro and in vivo, by means of isolated smooth muscle preparations and by measurements of blood pressure in anaesthetized rats, respectively. We demonstrate here that a pyroglutamyl residue at the N-terminus with a high content of proline residues, even with the presence of a IPP moiety characteristic of typical BPPs, are not enough to determine a bradykinin-potentiating activity to these peptides. Taken together, our results indicate that the characterization of the BPPs precursor proteins and identification of characteristic glutamine residues followed by proline-rich peptide sequences are not enough to predict if these peptides, even with a pyroglutamyl residue at the N-terminus, will present the typical pharmacological activities described for the BPPs.
Gomes
Claudiana L
CL
Center for Applied Toxinology, Instituto Butantan, São Paulo, SP, Brazil.
Konno
Katsuhiro
K
Conceição
Isaltino M
IM
Ianzer
Danielle
D
Yamanouye
Norma
N
Prezoto
Benedito C
BC
Assakura
Marina T
MT
Rádis-Baptista
Gandhi
G
Yamane
Tetsuo
T
Santos
Robson A
RA
de Camargo
Antonio C M
AC
Hayashi
Mirian A F
MA
D000595:Amino Acid Sequence; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D003001:Cloning, Molecular; D003435:Crotalid Venoms / Q000737:chemistry*; D017839:Crotalus / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D011498:Protein Precursors / Q000138:chemical synthesis / Q000235:genetics / Q000302:isolation & purification* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012469:Salivary Glands / Q000378:metabolism*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D003435:Crotalid Venoms; D009842:Oligopeptides; D011498:Protein Precursors; C006791:bradykinin potentiating factors