Comparative Study to Characterise the Pharmaceutical Potential of Synthesised Snake Venom Bradykinin-Potentiating Peptides In Vivo.

BACKGROUND: Bradykinin-potentiating peptides (BPPs) are snake venom peptides inhibiting the angiotensin-converting enzyme (ACE). ACE plays an important role in the regulation of blood pressure. BPPs lead to the development of ACE inhibitors for the treatment of hypertension. OBJECTIVE: The objective of the present work was to carry out a comprehensive comparative study of four synthesised snake venom BPPs in vivo. METHODS: Four synthesised snake venom BPPs were administered to rats via the intraperitoneal route for 15 days at a fixed dose. Lisinopril was used as a comparative standard. Thirty male albino rats were divided into six groups: A, B, C, D, E (lisinopril), and F (control). Group F was maintained as the control group and given only saline. After 15 days, blood samples and tissues were removed for the study of selective biochemical parameters and histomorphometric analysis. Statistical evaluation of all results was also performed. RESULTS: The results indicated that peptide I, with the sequence ZSAPGNEAIPP, was highly toxic and adversely affected all the biochemical and histological parameters studied in this work. Peptide II (ZNWPHPQIPP) and peptide IV (ZQWAQGRAPHPP) showed lower toxicity. None of the BPPs raised the serum creatinine level and exhibited nephroprotective effects. Although lisinopril raised the creatinine level, it showed a protective role towards the pancreas and lungs in parallel. CONCLUSION: The present work shows that although there is a high sequence similarity between the four BPPs, their in vivo activity varies. The sequences of peptide II and peptide IV can be used to improve the design of current ACE inhibitors used for hypertension treatment.

Evolution of Single Chain Conformation for Model Comb-Like Chains with Grafting Density Ranging from 0 to ∼100% in Dilute Solution.

This work aims to experimentally clarify how the single chain conformation evolves as a function of grafting density for model comb-like chains in dilute solution in the whole density regime. Via a combination of rational design, precise synthesis and accurate characterization, we obtained four sets of PPANb-g-PS30-σ comb-like samples with well-defined architectures and accurately extracted their molecular parameters by triple detection size exclusion chromatography (TD-SEC). With these samples in hand, we quantified how the excluded volume interaction and chain conformation evolve with the grafting density (σ) in the whole density regime. Three main findings are reported: (i) the graft-graft excluded volume interaction is not ignorable even in the low σ-regime; (ii) contrary to theoretical predictions, both the excluded volume interaction and the chain conformation are found to be Nb-dependent; (iii) both Rg ∼ σ1/3 and [η] ∼ σ0 are experimentally confirmed for comb-like chains from different σ and Nb, signifying a unique 3D mass-size growth pattern and a quasi-3D fractal feature. The obtained results help clarify some long-existed controversial issues in the field.