Structural Characterization and Rat Aortic Vascular Reactivity of Bradykinin-Potentiating Peptides (BPPs) from the Snake Venom of Bothrops moojeni from Delta do Parnaíba Region, Brazil.
Samuel R CostaAndreanne G VasconcelosJosé Otávio C S AlmeidaDaniel Dias Rufino ArcanjoAnderson DemateiEder A BarbosaPedro Costa SilvaThiago NascimentoLucianna H SantosPeter EatonJosé Roberto de Souza de Almeida LeiteGuilherme Dotto BrandPublished in: Journal of natural products (2024)
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.
Keyphrases
- angiotensin converting enzyme
- mass spectrometry
- angiotensin ii
- amino acid
- aortic valve
- high throughput
- left ventricular
- oxidative stress
- dna binding
- high resolution
- molecular dynamics
- binding protein
- drinking water
- molecular dynamics simulations
- molecular docking
- hiv infected
- coronary artery
- protein protein
- induced apoptosis
- pulmonary hypertension
- men who have sex with men
- simultaneous determination
- hiv testing
- oxide nanoparticles