Identification of novel bradykinin-potentiating peptides (BPPs) in the venom gland of a rattlesnake allowed the evaluation of the structure–function relationship of BPPs

详细信息	查看全文 | 推荐本文 |

• 作者：Claudiana L. Gomes ; Katsuhiro Konno ; Isaltino M. Conceiç ; ã ; o ; Danielle Ianzer ; Norma Yamanouye ; Benedito C. Prezoto ; Marina T. Assakura ; G ; hi Rá ; dis-Baptista ; Tetsuo Yamane ; Robson A. Sant
• 关键词：Snake venom ; Bradykinin-potentiating peptides ; ACE inhibitors ; Bioactive peptides ; Blood pressure ; Toxin
• 刊名：Biochemical Pharmacology
• 出版年：2007
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：1 November 2007
• 卷：74
• 期：9
• 页码：1350-1360
• 文件大小：1408 K

摘要

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.