Functional and structural characterization of a novel member of the natriuretic family of peptides from the venom of Pseudocerastes persicus

Abstract

A novel peptide, PNP (Pseudocerastes persicus natriuretic peptide), was isolated from the venom of the Iranian viper P. persicus. Amino acid sequencing revealed that the 37-residue peptide belongs to the family of natriuretic peptides. The physiological e¡ects of intra-venously PNP infused into anesthetized rats on urine £ow, sodium excretion and blood pressure were comparable to those of atrial natriuretic peptide (ANP). In PC12 cells that were treated with either PNP, ANP, or C-type natriuretic peptide, PNP induced a similar cGMP response as ANP. Since PC12 cells only express the natriuretic peptide receptor (NPR)-A receptor we conclude that PNP binds to the NPR-A receptor. The solution conformation of PNP was characterized using 1 H nuclear magnetic resonance spectroscopy and indicates a high degree of conformational £exi-bility.

Natriuretic peptides and therapeutic applications

“…Notably, antiplatelet activities have also been reported in a 37-residue peptide, Pseudocerastes persicus natriuretic peptide (PNP), which was isolated from the venom of the Iranian viper, Pseudocerastes persicus [103]. In addition, Michel et al [104] reported the isolation of two N-terminally truncated forms of CNP from the venom of Trimeresurus flavoviridis (habu snake): Tf-CNP (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and Tf-CNP (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) [104].…”

Backbone dynamics of oxidised and reduced forms of human atrial natriuretic peptide

“…By contrast, in flexible peptides 1 H a chemical shifts depend mostly on the nature of the attached sidechain, with the identity of neighbouring residues in the sequence having only small effects. After changes in solution conditions and amino acid composition are taken into account, the 1 H N and 1 H a chemical shifts of ANP ox differ little from those recorded in earlier studies of a hexamutant ANP variant (Fairbrother et al, 1994) and of more obviously random coil homologues including urodilatin, which has a 4 amino acid extension at the N-terminus (Weber et al, 1994), and PNP, a natriuretic peptide found in the venom of the snake Pseudocerastes persicus (Amininasab et al, 2004).…”

CHAPTER 5. Reptile Venoms as a Platform for Drug Development

“…40 The rst reptilian NP was isolated from the venom of the Eastern green mamba (Dendroaspis angusticeps), and was termed Dendroaspis natriuretic peptide (DNP). 44 Subsequently, reptilian NPs were puried from the venoms of Pseudocerastes persicus, 45 Oxyuranus microlepidotus, 46 Crotalus durissus cascavella (¼C. d. terricus), 47 Micrurus corallinus, 48 Bungarus avi-ceps, 49 and Agkistrodon halys blomhoffii (¼Gloydius blomhoffii blomhoffii).…”