Applications of Snake Venom Proline-Rich Oligopeptides (Bj- PROs) in Disease Conditions Resulting from Deficient Nitric Oxide Production

Abstract

Snake venoms contain a complex mixture of proteins and biologically active peptides [1, 2]. Some of these bioactive peptides are derived from precursor proteins that through proteolytic processing generate mature active polypeptides [3]. As an example, the protein precursor of natriuretic peptide type-C (CNP) from the Brazilian pit viper Bothrops jararaca venom and brain originates CNP, a hormone present in several animal species as well as various isoforms of proline-rich oligopeptides (Bj-PROs) [4, 5]. Bj-PROs were the first natural inhibitors of angiotensin I-converting enzyme (ACE) described [6]. The metalloproteinase ACE, the key enzyme of the renin-angiotensin system, displays two homologous active sites, one at the C-terminal and the other at the N-terminal of the protein [7]. While both active sites convert angiotensin I into angiotensin II and cleave bradykinin (BK) into BK1-5 and BK1-7, the C-terminal is more effective in hydrolysis of these vasoactive peptides [8]. Bj-PROs are molecules of 5 to 14 amino acids residues with a pyroglutamyl residue (