title: Leucurogin, a new recombinant disintegrin cloned from Bothrops leucurus (white-tailed-jararaca) with potent activity upon platelet aggregation and tumor growth.
abstract: Disintegrins and disintegrins-like proteins are able to inhibit platelet aggregation and integrin-mediated cell adhesion. The aim of this study was to produce one disintegrin-like cloned from Bothrops leucurus venom gland and to characterize it regarding biological activity. The recombinant protein was purified by one step procedure involving anion-exchange chromatography (DEAE-cellulose) and presented a molecular mass of 10.4 kDa. The purified protein was able to inhibit platelet aggregation induced by collagen (IC₅₀ = 0.65 μM) and to inhibit growth of Ehrlich tumor implanted in mice by more than 50% after 7 days administration of 10 μg/day. No effects were observed upon adenosine 5'-diphosphate (ADP)-and arachidonic acid (AA)-induced platelet aggregation. The recombinant protein was recognized by an antibody specific for jararhagin one metalloproteinase isolated from Bothrops jararaca venom, and therefore it was named leucurogin. Anti-angiogenesis effect of leucurogin was evaluated by the sponge implant model. After 7 days administration leucurogin inhibited, in a dose dependent way, the vascularization process in the sponge. Leucurogin represents a new biotechnological tool to understand biological processes where disintegrins-like are involved and may help to characterize integrins that can be involved in development and progression of malignant cells.
authors.affiliation: Universidade de Mogi das Cruzes, Av. Dr Cândido Xavier de Almeida e Souza 200, Centro Cívico, 08780-911 Mogi das Cruzes, São Paulo, Brazil.
authors.forename: D A
authors.initials: DA
authors.lastname: Higuchi
authors.forename: M C
authors.initials: MC
authors.lastname: Almeida
authors.forename: C C
authors.initials: CC
authors.lastname: Barros
authors.forename: E F
authors.initials: EF
authors.lastname: Sanchez
authors.forename: P R
authors.initials: PR
authors.lastname: Pesquero
authors.forename: E A S
authors.initials: EA
authors.lastname: Lang
authors.forename: M
authors.initials: M
authors.lastname: Samaan
authors.forename: R C
authors.initials: RC
authors.lastname: Araujo
authors.forename: J B
authors.initials: JB
authors.lastname: Pesquero
authors.forename: J L
authors.initials: JL
authors.lastname: Pesquero
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D017837:Bothrops / Q000235:genetics / Q000378:metabolism*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D003001:Cloning, Molecular; D003435:Crotalid Venoms; D019483:Disintegrins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008666:Metalloendopeptidases; D051379:Mice; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology*; D016415:Sequence Alignment; D000097146:Bothrops jararaca Venom
chemical_list: D020533:Angiogenesis Inhibitors; D003435:Crotalid Venoms; D019483:Disintegrins; D008666:Metalloendopeptidases; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D000097146:Bothrops jararaca Venom