Selective Inhibition of the C-Domain of Angiotensin I Converting Enzyme by Bradykinin Potentiating Peptides

Cotton, J. P.; Hayashi, Mirian A. F.; Cuniasse, Philippe; Vazeux, Gilles; Ianzer, Danielle; Camargo, and Antonio C. M. De; Dive, Vincent

doi:10.1021/bi012121x

Cited by 83 publications

(102 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the snake venom bradykinin potentiating peptide BPPb has the sequence Glu-Gly-Leu-Pro-Pro-Arg-Pro-LysIle-Pro-Pro, whereas the peptide BPPc has the sequence Glu-Gly-Leu-Pro-Pro-Gly-Pro-Pro-Ile-ProPro. Despite this small difference, BPPb exhibits K i values of 10,000 and 30 nM for the ACE N-and Cdomains, respectively, whereas BPPc has a K i of 80 nM for both the N-and C-domains (Cotton et al, 2002). Thus, relatively small changes can make an enormous difference in domain selectivity.…”

Section: Domain-specific Inhibitorsmentioning

confidence: 97%

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

et al. 2012

View full text Add to dashboard Cite

Section: Domain-specific Inhibitorsmentioning

confidence: 97%

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

et al. 2012

View full text Add to dashboard Cite

“…Keto-ACE, originally described in 1980, was found to exhibit a 40-to 50-fold C-selectivity. 195 One of the bradykinin potentiator peptides, BPPb, was shown to be 300-fold more C-selective, 200 and the phosphinic tetrapeptide RXPA380 is 3000-fold more C-selective. 190 However, BPP-12b is 30-fold more N-selective, and the phosphinic tetrapeptide RXP407 is 1000-fold more N-selective [201][202][203] (Figure 3).…”

Section: Future Of Aceismentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

View full text Add to dashboard Cite

Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

show abstract

“…The inhibitions of somatic ACE determined for Bj-BPP-7a were performed as previously described (Cotton et al, 2002). In summary, the synthetic BPP was dissolved in buffer containing either the Mca-Ala or Mca-Ser substrate.…”

Section: In Vitro Assay: Enzyme Assays For Selective Inhibition Of Thmentioning

confidence: 99%

“…Three reasons explain the renewed interest: a number of the Bj-BPPs can distinguish between the N and C active sites of sACE (Cotton et al, 2002). In fact, sACE has two homologous and functionally distinct active sites (Wei et al, 1991), one of which, the active site at the C domain (C site), is slightly more effective in hydrolyzing some vasoactive peptides, like bradykinin and angiotensin I (Perich et al, 1992;Jaspard et al, 1993); 2) the isolation and identification of novel Bj-BPPs in the crude venom (Ianzer et al, 2004); and 3) the presence of several Bj-BPPs in the C-type natriuretic peptide precursor of the snake brain may reveal novel neuropeptides (Murayama et al, 1997;Hayashi et al, 2003).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Do the Cardiovascular Effects of Angiotensin-Converting Enzyme (ACE) I Involve ACE-Independent Mechanisms? New Insights from Proline-Rich Peptides ofBothrops jararaca

Ianzer

Santos²,

Etelvino³

et al. 2007

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Angiotensin-converting enzyme (ACE) inhibitors were developed based on proline-rich oligopeptides found in the venom of Bothrops jararaca (Bj) previously known as bradykinin-potentiating peptides (BPPs). However, the exact mechanism of action of BPPs remains unclear. The role of the ACE in the cardiovascular effects of two of naturally proline-rich oligopeptides (Bj-BPP-7a and Bj-BPP-10c) was evaluated in vitro and in vivo. Bj-BPP-7a does not potentiate the cardiovascular response to bradykinin and is a weak inhibitor of ACE C and N sites (K i ϭ 40,000 and 70,000 nM, respectively), whereas Bj-BPP-10c is a strong bradykinin potentiator and inhibitor of the ACE C site (K i ϭ 0.5 versus 200 nM for N site). Strikingly, both peptides, in doses ranging from 0.47 to 71 nmol/kg, produced long-lasting reduction (Ͼ6 h) in the mean arterial pressure of conscious spontaneously hypertensive rats (maximal change, 45 Ϯ 6 and 53 Ϯ 6 mm Hg for Bj-BPP-7a and Bj-BPP-10c, respectively). The fall in blood pressure was accompanied by variable degrees of bradycardia. In keeping with the absence of relationship between ACE-inhibitory and antihypertensive activities, no changes in the pressor effect of angiotensin I or in the hypotensive effect of bradykinin were observed at the peak of the cardiovascular effects of both peptides. Our results indicate that the antihypertensive effect of two Bj-BPPs containing the motif Ile-Pro-Pro is unrelated to their ability for inhibiting ACE or potentiating bradykinin (BK), indicating as a major component ACE and BK-independent mechanisms. These results are in line with previous observations suggesting ACE inhibition-independent mechanisms for angiotensin I-converting enzyme inhibitor.

show abstract

Selective Inhibition of the C-Domain of Angiotensin I Converting Enzyme by Bradykinin Potentiating Peptides

Cited by 83 publications

References 35 publications

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

Do the Cardiovascular Effects of Angiotensin-Converting Enzyme (ACE) I Involve ACE-Independent Mechanisms? New Insights from Proline-Rich Peptides ofBothrops jararaca

Contact Info

Product

Resources

About