| Autor: |
Costa SR; Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Universidade de Brasília, Brasília 70910-900, Brazil., Vasconcelos AG; Núcleo de Pesquisa em Morfologia e Imunologia Aplicada (NuPMIA), Faculdade de Medicina, Universidade de Brasília, Brasília 70910-900, Brazil., Almeida JOCS; LAFMOL-Laboratório de Estudos Funcionais e Moleculares em Fisiofarmacologia, Departamento de Biofísica e Fisiologia, Universidade Federal do Piauí, Teresina 64049-550, Brazil., Arcanjo DDR; LAFMOL-Laboratório de Estudos Funcionais e Moleculares em Fisiofarmacologia, Departamento de Biofísica e Fisiologia, Universidade Federal do Piauí, Teresina 64049-550, Brazil., Dematei A; Núcleo de Pesquisa em Morfologia e Imunologia Aplicada (NuPMIA), Faculdade de Medicina, Universidade de Brasília, Brasília 70910-900, Brazil., Barbosa EA; Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Universidade de Brasília, Brasília 70910-900, Brazil., Silva PC; Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Universidade Federal do Delta do Parnaíba, UFDPAR, Parnaíba, Piauí 64202-020, Brazil., Nascimento T; Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Universidade Federal do Delta do Parnaíba, UFDPAR, Parnaíba, Piauí 64202-020, Brazil., Santos LH; Biomolecular Simulations Group, Institut Pasteur de Montevideo, Montevideo 11400, Uruguay., Eaton P; The Bridge, Joseph Banks Laboratories, School of Chemistry, University of Lincoln, Lincoln LN6 7EL, U.K., Leite JRSA; Núcleo de Pesquisa em Morfologia e Imunologia Aplicada (NuPMIA), Faculdade de Medicina, Universidade de Brasília, Brasília 70910-900, Brazil.; Núcleo de Pesquisa em Biodiversidade e Biotecnologia, Biotec, Universidade Federal do Delta do Parnaíba, UFDPAR, Parnaíba, Piauí 64202-020, Brazil., Brand GD; Laboratório de Síntese e Análise de Biomoléculas, LSAB, Instituto de Química, Universidade de Brasília, Brasília 70910-900, Brazil. |
| Abstrakt: |
Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico . A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators. |
