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ABSTRACT: Various aminopeptidases belong to the M1 aminopeptidase family. They are all zinc dependent enzymes playing important roles in several biological processes such as regulation of blood pressure under both physiological and pathological conditions, and the angiogenesis and metastasis of tumor, etc. They all have the highly conserved HEXXH(X)18E zinc-binding and GAMEN motifs essential for enzyme activities. In this review, the current situation regarding the biochemical characteristics, biological functions and inhibitors of three important members of these enzymes, aminopeptidase A, aminopeptidase N and aminopeptidase B are summarized.
Current Protein and Peptide Science 08/2012; 13(5):490-500. · 2.89 Impact Factor
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ABSTRACT: Aminopeptidase N (APN/CD13) of the M1 family is a broad specificity enzyme that is intimately involved in tumor angiogenesis and metastasis. Asparagine-glycine-arginine (NGR) is a tumor-homing tripeptide, which can selectively combine with APN/CD13 that is overexpressed on the surface of some tumor cells. Various anti-tumor drugs can be conjugated to NGR to improve selectivity, efficacy, and to decrease drug toxicity. In this study, a tripeptide NGR(NO2) was synthesized and conjugated with 5-fluorouracil. The anti-tumor activities of this new prodrug were evaluated in vivo. More significant anti-tumor effects were observed over the parent 5-fluorouracil.
Protein and Peptide Letters 04/2012; 19(10):1122-31. · 1.94 Impact Factor
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Yepeng Luan,
Chunhua Ma,
Zhongguo Sui,
Xuejian Wang,
Jinhong Feng,
Ning Liu,
Fanbo Jing,
Yan Wang,
Minyong Li,
Hao Fang,
Wenfang Xu
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ABSTRACT: Aminopeptidase N (APN) is a ubiquitous enzyme overexpressed on tumor cells and plays an important role in angiogenesis and metastasis of tumor. Bestatin as an effective inhibitor of aminopeptidase N is used for complementary treatment of cancer with other drugs. In this work, we reformed the structure of bestatin to a new derivative LYP3 to improve the water solubility and effectiveness. The inhibitory activity of LYP3 against APN was evaluated in vitro.
Medicinal chemistry (Shāriqah (United Arab Emirates)) 01/2011; 7(1):32-6. · 1.64 Impact Factor
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ABSTRACT: As a ubiquitous enzyme overexpressed on the epithelium of the tumor, aminopeptidase N (APN) plays important roles in the angiogenesis and metastasis of the tumor. Bestatin as an effective inhibitor against APN is used in the ancillary treatment of various cancers. In this study, we modified the structure of a bestatin derivative LYP reported in our former study to provide a new bestatin derivative LYP2 with enhanced stability. We also tested the inhibitive activity of LYP2, which retained good efficacy in vitro and in vivo towards APN.
Anti-cancer drugs 11/2010; 22(1):99-103. · 2.23 Impact Factor
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Qiang Wang,
Fuming Xu,
Jiajia Mou,
Jian Zhang,
Luqing Shang, Yepeng Luan,
Yumei Yuan,
Yingzi Liu,
Minyong Li,
Hao Fang,
Binghe Wang,
Wenfang Xu
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ABSTRACT: A novel class of L-lysine derivatives as aminopeptidase N (APN) inhibitors was designed and synthesized. Activity evaluation showed that compound C7 (IC50 = 9.6 ± 1.3 μM) and C20 (IC50 = 13.6 ± 1.9 μM) were equivalent to the positive control Bestatin (IC50 = 11.3 ± 1.6 μM).
Protein and Peptide Letters 06/2010; 17(7):847-853. · 1.94 Impact Factor
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Qiang Wang,
Fuming Xu,
Jiajia Mou,
Jian Zhang,
Luqing Shang, Yepeng Luan,
Yumei Yuan,
Yingzi Liu,
Minyong Li,
Hao Fang,
Binghe Wang,
Wenfang Xu
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ABSTRACT: A novel class of L-lysine derivatives as aminopeptidase N (APN) inhibitors was designed and synthesized. Activity evaluation showed that compound C7 (IC(50) = 9.6 +/-1.3 microM) and C20 (IC(50) = 13.6 +/- 1.9 microM) were equivalent to the positive control Bestatin (IC(50) = 11.3 +/- 1.6 microM).
Protein and Peptide Letters 02/2010; 17(7):847-53. · 1.94 Impact Factor
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ABSTRACT: Aminopeptidase N (APN) is a ubiquitous enzyme overexpressed on the epithelium of tumor and plays an important role in angiogenesis and metastasis of tumor. Bestatin acting as an inhibitor of Aminopeptidase N and B is used in the ancillary treatment of cancer. In this paper, we designed, synthesized a derivative of Bestatin (LYP), and evaluated the activity of it which exhibited better efficacy than Bestain in vitro and vivo.
Letters in Drug Design & Discovery 08/2009; 6(6):420-423. · 0.87 Impact Factor
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ABSTRACT: Bestatin, (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine, is an effective inhibitor of the aminopeptidase N and other leucine and arginine aminopeptidases , having the selectivity toward the Aminopeptidase N (APN) and the Aminopeptidase B (APB) which are all metalloproteases belonging to the M1 aminopeptidase family. In spite of the poor selectivity and toxicity, so far, Bestatin is still the only marketed inhibitor of APN for cancer treatment. Considering that the inhibitor of APN is a promising agent to control and treat cancer, many efforts have been made to curtail the whole synthesis of the Bestatin and this mini-review will introduce the whole synthesis of Bestatin.
Mini-Reviews in Organic Chemistry 04/2008; 5(2):134-140. · 2.41 Impact Factor
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ABSTRACT: Aminopeptidase N (APN)/CD13 is a type II metalloprotease that belongs to the M1 family of the MA clan, which consists of 967 amino acids with a short N-terminal cytoplasmic domain, a single transmembrane part, and a large cellular ectodomain containing the active site. APN has a molecular weight of 110,000. The APN exists in two forms, namely the membrane aminopeptidase N and the soluble aminopeptidase N. Moreover, it exhibits the presence of various isozymes with different functions. APN is a ubiquitous enzyme present in a wide variety of human organs, tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). It is a multifunctional enzyme, related with tumorigenesis, immune system, pain etc. Furthermore, it also serves as a receptor for coronaviruses and other human viruses. Besides the manifestation of various other functions, APN is also involved in the trimming of antigen and the process of antigen presentation. These functions facilitate the modulation of bioactive peptide responses (pain management, vasopressin release) and influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis) thereby providing treatment options for many kinds of diseases. This review will introduce the structure and main functions of APN briefly.
Current Medicinal Chemistry 02/2007; 14(6):639-47. · 4.86 Impact Factor
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ABSTRACT: Cyclooxygenase plays a pivotal role in the transformation of the arachidonic acid to prostaglandins (PGs) and thromboxane. It is composed of two kinds of enzymes, namely cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). Cyclooxygenase 1 is the constructive enzyme whereas the cyclooxygenase 2 is the inducible enzyme. Inhibiting cyclooxygenase 1 is always associated with some undesirable side-effects, while inhibiting cyclooxygenase 2 can result in therapeutic effect. This has led the researchers to strive for searching the selective inhibitors inhibiting the COX-2 instead of COX-1. It is very well known that pain and inflammation are alleviated through the inhibition of COX-2 inhibitors such as Aspirin, which has resulted in the recent years, in the emergence of a range of COX-2 inhibitors. Moreover, while evaluating the functions of the COX-2 inhibitions, their significant role in treating glaucoma, preventing and suppressing cancer through their inhibitory activity was clearly revealed and many studies further demonstrated that COX-2 is not only related to the inflammation of peripheral tissues but also to the inflammation manifested in the central nervous system. In addition, the nervous disorders also found an effective treatment with the administration of COX-2 inhibitors. The above-mentioned findings delineate the role of the COX-2 inhibitors as promising agents to be exploited in the treatment of many illnesses. This review will elucidate the functions of the COX-2 inhibitors briefly and introduce some common selective inhibitors of COX-2.
Mini Reviews in Medicinal Chemistry 01/2007; 6(12):1375-81. · 2.53 Impact Factor
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ABSTRACT: Cyclooxygenase plays a pivotal role in the transformation of the arachidonic acid to prostaglandins (PGs) and thromboxane. It is composed of two kinds of enzymes, namely cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX- 2). Cyclooxygenase 1 is the constructive enzyme whereas the cyclooxygenase 2 is the inducible enzyme. Inhibiting cyclooxygenase 1 is always associated with some undesirable side-effects, while inhibiting cyclooxygenase 2 can result in therapeutic effect. This has led the researchers to strive for searching the selective inhibitors inhibiting the COX-2 instead of COX-1. It is very well known that pain and inflammation are alleviated through the inhibition of COX-2 inhibitors such as Aspirin, which has resulted in the recent years, in the emergence of a range of COX-2 inhibitors. Moreover, while evaluating the functions of the COX-2 inhibitions, their significant role in treating glaucoma, preventing and suppressing cancer through their inhibitory activity was clearly revealed and many studies further demonstrated that COX-2 is not only related to the inflammation of peripheral tissues but also to the inflammation manifested in the central nervous system. In addition, the nervous disorders also found an effective treatment with the administration of COX-2 inhibitors. The above-mentioned findings delineate the role of the COX-2 inhibitors as promising agents to be exploited in the treatment of many illnesses. This review will elucidate the functions of the COX-2 inhibitors briefly and introduce some common selective inhibitors of COX-2.
Mini Reviews in Medicinal Chemistry 11/2006; 6(12):1375-1381. · 2.53 Impact Factor
