Novel Peptides In The Venoms Of Rattlesnake

^{1Higuchi, S.; 1}Murayama, N.; ¹Saguchi, K.; ¹Ohi, H.; ¹Fujita, Y.; ²da Silva, Jr., N.J. and ³Aird, S.D.

1 Showa University School of Pharmaceutical Sciences, JAPAN; 2 Centro de Estudos e Pesquisas Biológicas, Universidade Católica de Goiás, BRASIL; 3 Department of Chemistry, Norfolk State University, USA

Sequencing of a cDNA clone from B. jararaca revealed that it encodes a precursor polypeptide bearing angiotensin converting enzyme inhibitors (ACEIs, also known as bradykinin potentiating peptides (BPPs)) at the N-terminus and a C-type natriuretic peptide (CNP) at the C-terminus (1). Findings that most crotaline snakes have homologous genes for the ACEI/BPP-CNP precursor strongly suggest that their venoms contain both ACEIs/BPPs and CNPs (2). Analysis of the ACEI/BPP-CNP cDNA from Crotalus durissus collilineatus has shown a sequence TPPAGPDGGPR (1020.5 Da) in the precursor molecule, in addition to the sequences for ACEI/BPP and CNP. Fractionation of the crude venom by reversed phase HPLC (C18), and analysis of the fractions by mass spectrometry indicated a component with the same molecular mass and sequence. The previously isolated peptide TPPAGPDVGPR by Aird from Crotalus v. viridis venom has an identical sequence except valine residue at the 8th position, suggesting that it must be derived from the gene responsible for ACEIs/BPP and CNP. Their high proline content and paired proline residues are typical of venom hypotensive peptides, although it lacks the usual N-terminal pyroglutamate. The pharmacological activity of these peptides has not yet been determined; however, its occurrence in the venoms of two dissimilar species suggests that its presence is not accidental. By applying the same strategy, the search for novel peptides is in progress with the venoms of various rattlesnakes.

References:

1. Murayama, N. et al, PNAS 1997, 94, 1189-1193.

2. Higuchi, S. et al, Immunopharmacology 1999, 44, 129-135.

Correspondence to: higuchis@pharm.showa-u.ac.jp