Bradykinin-Potentiating Peptides (BPP)

Introduction

Bradykinin-potentiating peptides are proline-rich peptides known to inhibit angiotensin-converting enzyme (ACE). This enzyme is responsible for the conversion of angiotensin I to angiotensin II. Angiotensin II is an effective vasoconstrictor and hypertension agent. The first bradykinin-potentiating peptide was discovered by Ferreira and Rocha e Silva and termed as such due to its pharmacological effect, i.e., literally potentiate/enhance the effect of bradykinin (BK), in comparison to the same BK dose administered prior to the bradykinin-potentiating peptide treatment, without presenting any hypotensive effect. Since then, bio-driven assays have found several bradykinin-potentiating peptides from many sources, such as scorpion venom, tree frog skin secretions, and snake venom from other species. Snake bradykinin-potentiating peptides are mostly less than 14-mer proline-rich peptides, presenting three distinct features. The first one is an almost invariable pyroglutamic acid at the N-terminus. The second is the presence of a Pro residue at the C-terminus for peptides containing up to five residues The third is the presence of the tripeptide Ile-Pro-Pro at the C-terminus of less than 5-mer peptides containing up to 14 residues.

Mechanism of action

Bradykinin-potentiating peptides’ biological properties are associated with impairment of angiotensin II generation and bradykinin degradation. By inhibiting ACE, BPPs inhibit the formation of angiotensin II and lower blood pressure. In addition, since this enzyme is also capable of cleaving bradykinin, a hypotensive peptide, its inhibition involves two different mechanism targets (angiotensin and bradykinin), causing a comprehensive antihypertensive effect. After administration, the global physiological effect of the bradykinin-potentiating peptide is the decrease of the blood pressure.

Application of Bradykinin-Potentiating Peptides

Because of the interesting effect of bradykinin-potentiating peptides, David Cushman et al use one of these peptides to develop blood pressure lowering drugs, and the well-known captopril is widely used in the treatment of hypertension. From that time on, many studies on bradykinin-potentiating peptides have been conducted, basically describing new peptides and assaying their pharmacological effects, mostly in comparison to captopril. Therefore, Bradykinin-potentiating Peptides will be an ideal treatment for high blood pressure.

Reference

1. Habermehl, G.G., M?llring, Th., Coelfen, A., Ferreira, L.A.F. (1995). Bradykinin-potentiating peptides in snake venoms. Toxicon, 33(3), 257-258.