A NOVEL PEPTIDE FROM THE VENOMOUS MOLLUSK Conus regius

Braga, M.C.V.(1), Cassola, A.C.(2), Freitas, J.C.(1), Olivera, B.M.(3)

(1)IB, USP, São Paulo, SP, Brazil, (2)ICB, USP, (3)Dept. Biology, University of Utah, UT, USA. 

Conusisa genus of carnivorous mollusks that paralyze their prey by injecting a complex mixture of biologically active peptides that interact with receptors and ion channels. As no Brazilian species have been studied so far, and as each species has a wide variety of novel peptides with pharmacological interest, we have initiated a characterization of peptides in the Conus regius venom. This abstract will describe a primary structure of a new peptide, its neurotoxic effect and its blocking effect on K⁺ and Na⁺ voltage-dependent channels. Conus regius venom was purified by HPLC, its major component was sequenced and its mass spectrum was measured by MALDI-TOF. The sequence revealed a 43 amino acid peptide (4,688 Da) with four disulfide cross-links. The biological activity of the purified peptide was tested by intracranial injection in mice. The higher the concentration injected, the more sensitive to touch the animals became. The pattern of cysteines (C-C-CC-CC-C-C) with four disulfide cross-links and the excitatory effects characterize a new group of the conotoxins, the “I superfamily” (Shettyet al., unpublished results), in which this Conus regius peptide can be included. The activity of this peptide on K⁺ and Na⁺ voltage-dependent conductances of the somata of neurons in rat dorsal root ganglion was tested by patch-clamp experiments, in the whole-cell configuration. In high concentrations (mM range), the toxin reduced both currents, indicating that it is an unspecific blocker of K⁺ and Na⁺ voltage-dependent channels in mammal cells. Further research is in course in order to characterize the action of the Conus regius I-conotoxin.

Financial support: FAPESP

Acknowledgments: IBAMA, Águas Claras Diving Center, CEBIMAR-USP and University of Utah

CORRESPONDENCE TO:

Maria Cristina Vianna Braga, Alameda dos Arapanés 309, Apto. 22, São Paulo, SP, CEP: 04524-000, Brasil, Email: mcbraga@usp.br