Angiotensin-Converting Enzyme and the Regulation of Vasoactive Peptides

Soffer, Richard L.

doi:10.1146/annurev.bi.45.070176.000445

Cited by 447 publications

(159 citation statements)

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“…ACE plays an essential role in the renin-angiotensin system (RAS), which regulates both arterial blood pressure and the salt/water balance [24,25] . Since the first generation of ACE inhibitors was discovered from snakes, inhibitors of ACE have been a major target for discovering anti-hypertensive drugs [26][27][28][29] .…”

Section: Target Preparationmentioning

confidence: 99%

Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets

Chen

Zhang

et al. 2009

Acta Pharmacol Sin

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Aim: This study was conducted to compare the efficiencies of two virtual screening approaches, pharmacophore-based virtual screening (PBVS) and docking-based virtual screening (DBVS) methods. Methods: All virtual screens were performed on two data sets of small molecules with both actives and decoys against eight structurally diverse protein targets, namely angiotensin converting enzyme (ACE), acetylcholinesterase (AChE), androgen receptor (AR), D-alanyl-D-alanine carboxypeptidase (DacA), dihydrofolate reductase (DHFR), estrogen receptors α (ERα), HIV-1 protease (HIV-pr), and thymidine kinase (TK). Each pharmacophore model was constructed based on several X-ray structures of protein-ligand complexes. Virtual screens were performed using four screening standards, the program Catalyst for PBVS and three docking programs (DOCK, GOLD and Glide) for DBVS. Results: Of the sixteen sets of virtual screens (one target versus two testing databases), the enrichment factors of fourteen cases using the PBVS method were higher than those using DBVS methods. The average hit rates over the eight targets at 2% and 5% of the highest ranks of the entire databases for PBVS are much higher than those for DBVS. Conclusion: The PBVS method outperformed DBVS methods in retrieving actives from the databases in our tested targets, and is a powerful method in drug discovery. discovery, especially in the cases when no three-dimensional (3D) structural information on the protein target of interest is available. Even when the 3D structures of targets are known, PBVS is also used as a complementary approach to DBVS for pre-processing databases (libraries) of small molecules to remove compounds not possessing features known to be essential for binding or for post-filtering compounds selected by docking approaches [5] . A recent case study by Muthas et al indicated that post-filtering with pharmacophores was shown to increase enrichment rates in their investigated targets compared with docking alone [6] . Several studies have been performed to assess various DBVS methods and compare which docking programs are the most successful in identifying active hits [7][8][9][10] . The conclusion is that no docking program may outperform other docking programs for all the tested targets, and the performance of each tested docking program is highly dependent on the nature of the target binding site [5] .Nevertheless, few case studies for a direct comparison on the performances between PBVS and DBVS have been reported [11] . To gain a general view for the discrimination between these two types of approach in prioritizing actives from a database with decoys, we performed a benchmark comparison between the performances of PBVS and DBVS. Eight structurally diverse protein targets were selected in this study. The pharmacophore models were generated from the ligand co-crystallized complex structures of these targets using the LigandScout program [12] , and each PBVS was performed using the program Catalyst [13,14] . To avoid the target dependency of docking pro...

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Section: Target Preparationmentioning

confidence: 99%

Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets

Chen

Zhang

et al. 2009

Acta Pharmacol Sin

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“…Although the enzyme is always found in endothelial cells, the greatest amount and activity occurs in the endothelium of lungs (Soffer, 1976).…”

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confidence: 99%

Serum angiotensin-converting enzyme in malignant lymphomas, leukaemia and multiple myeloma

Rømer¹,

Emmertsen²

1980

Br J Cancer

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Serum angiotensin-converting enzyme (SACE) was analysed in 27 patients with Hodgkin's disease, 25 with non-Hodgkin lymphoma, 14 with acute leukaemia, 15 with chronic leukaemia, and 15 with multiple myeloma. SACE was depressed in these patients as a whole, with a mean level of 19.9 mu/ml, compared with 116 healthy controls (mean 24.4 mu/ml, P < 0.001). This depression was greatest in chronic leukaemia and multiple myeloma. In Hodgkin's disease no relationship was found between enzyme activity and stage, activity, histopathology, treatment, mediastinal involvement or prognosis. In non-Hodgkin patients a poor prognosis was generally associated with low SACE activity. The low SACE activity was not related to recent corticosteroid treatment, and the cause and pathophysiological significance is unexplained. Since SACE is high in the granulomatous disorder sarcoidosis (which can mimic malignant lymphnode and blood diseases) SACE analysis can be valuable in evaluating patients with mediastinal lymphadenopathy and those in whom non-caseating epitheliod granulomas are found.

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“…Angiotensin-1-converting enzyme (ACE, EC 3.4.15.1) is a zinc-metalloprotease that is detectable in all tissues and body fluids of mammals. 110 The activity of ACE is more than 50 times higher in seminal plasma than in serum and a majority of the seminal activity is membranebound to prostasomes. 111 ACE catalyses the conversion of a decapeptide, angiotensin I into the octapeptide, angiotensin II by splitting off the C-terminal dipeptide.…”

Section: Invasive Supportmentioning

confidence: 99%

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

Ronquist

Nilsson

2004

Prostate Cancer Prostatic Dis

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Prostasomes are submicron secretory granules synthesized, stored and secreted by the epithelial cells of the human prostate gland. They are membrane-surrounded also in their extracellular appearance and the membrane architecture is composite. They are believed to be life-giving and act as protectors of the spermatozoa in the lower and upper female genital tract on their way to the ovum. Hence, the prostasomes are immunosuppressive and inhibitory of complement activation. Further, they promote sperm's forward motility and have antioxidant and antibacterial capacities. The prostasomes with their many composite abilities seem to turn against the host cell after the age of 50 y being conducive to the transition of the normal prostate epithelial cell into a neoplastic cell and therewith lay the foundations of the very high prevalence of prostate cancer of men of more than 50 y of age. Prostate Cancer and Prostatic Diseases (2004) 7, 21-31. doi:10.1038/sj.pcan.4500684 Keywords: prostasomes Prostate cancerProstate cancer is the most common cancer in men in Europe, North America, and some parts of Africa. Incidence of prostate cancer is increasing steadily in most countries. Incidence and death rates differ according to race and geographical location. 1 Different autopsy studies performed in Western and Oriental populations have shown that the prevalence of prostate cancer is significantly higher than its incidence. Comparative assessments of these studies have provided similar prevalence rates in different races and geographical areas. 2 The differences in the incidence of prostate cancer in different races and geographical areas and the different progression of this incidence in populations of a race living in a foreign geographical area, strengthen the hypothesis that genetic and lifestyle factors are responsible for the difference in post-induction progression of prostate cancer. 3,4 The incidence rate of clinically apparent prostate cancer is eight-fold higher in the United States than in Japan, while the prevalence of latent prostate cancer, a presumed precursor of clinical prostate cancer, is similar in the two countries. 5 However, the initiating and promoting factors that determine the variability in the natural history of prostate cancer remain unknown. 6 There is a substantial discrepancy between the high incidence of prostate cancer and the extremely low incidence of primary cancer in the seminal vesicles, 7 although the two glands represent neighbouring anatomical locations, both of them being exocrine accessory genital glands and both being under similar hormonal control. Hence, there may be endogenous as well as exogenous factors promotive of prostate cancer development. We hypothesize that prostasomes with their exclusive origin in the prostate gland and with their Received

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Angiotensin-Converting Enzyme and the Regulation of Vasoactive Peptides

Cited by 447 publications

References 0 publications

Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets

Pharmacophore-based virtual screening versus docking-based virtual screening: a benchmark comparison against eight targets

Serum angiotensin-converting enzyme in malignant lymphomas, leukaemia and multiple myeloma

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

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