Bradykinin-potentiating peptide family

(or proline-rich peptide family)

General Activity
Bradykinin-potentiating peptides (BPPs) are short peptides only found in venoms of snakes and spiders and in amphibian skin secretions. They potentiate the hypotensive cardiovascular response to bradykinin (for a description of this peptide, see bradykinin-related peptide family). However, the exact mechanism of action of BPPs remains unclear. Some of them inhibit somatic angiotensin-converting enzyme (ACE) , a vasoconstrictor that converts angiotensin-1 to angiotensin-2 and degrades bradykinin. Other BPPs display a strong and sustained anti-hypertensive effect by a pharmacological effect independent of ACE inhibition. As examples, the snake peptide BPP-10c is the most selective inhibitor of the active site at the C-domain of ACE, and displays a strong and sustained anti-hypertensive effect independently of the inhibition of ACE. This peptide has been described as being a direct activator of the intracellular argininosuccinate synthase, an enzyme implicated in different cycles, including the citrulline-nitric oxide (NO) cycle that represents a potential limiting step in NO synthesis (Guerreiro et al., 2009). In another study, this is the NO production induced by BPPs that explains hypotension. Indeed, BPP-5a increases NO production in HEK293 cell line, which is mediated by the two receptors bradykinin receptors B2 and muscarinic acetylcholine receptor M1 (Morais et al., 2011).

Sequence characteristics
The most characteristic structural features of this family is the short size of the peptides (5-13 amino acid residues), an invariable N-terminal pyroglutamate residue (pGlu or Z) and two consecutive proline residues at the C-terminus.

The chemical and pharmacological properties of BPPs were essential for the development of captopril (wikipedia, DrugBank), the first active site directed inhibitor of ACE, currently used to treat human hypertension.