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排序方式: 共有349条查询结果,搜索用时 15 毫秒
101.
目的 寻找具有氨肽酶N(APN,CD13)抑制活性的新型化合物并测定其抑制氨肽酶N的活性;考察目标化合物与APN活性位点的结合,研究目标化合物与酶的相互作用关系。方法 以光学纯的天冬酰胺为原料,经Boc保护、环合、酯化、脱Boc保护、酰化、氢化还原、羟肟酸化等反应合成目标化合物。借助FlexX对接软件,研究目标化合物与APN活性位点的结合情况;采用体外抑酶试验测定目标化合物抑制APN的活性。结果 合成了14个未见文献报道的 N-取代-2,5-吡咯烷二酮类肽类APN抑制剂,其结构经1H-NMR、MS谱确证。结论 目标化合物均对APN/CD13具有一定的抑制活性,其中,化合物7h的活性较好,与计算机对接结果一致。 相似文献
102.
One of the fragments of the cardiovascular hormone Angiotensin II incited the interest of several research groups. This 3–8 fragment, denoted as Angiotensin IV (Ang IV) causes a number of distinct biological effects (see Introduction), unlikely to be explained by its weak binding to AT1 and/or AT2 receptors. Moreover the discovery of high affinity [125I]-Ang IV binding sites and their particular tissue distribution led to the concept of the AT4 receptor. An important breakthrough was achieved by defining the AT4 receptor as the membrane-bound insulin-regulated aminopeptidase (IRAP). Crucial for the definition as a receptor the binding of the endogenous ligand(s) should be linked to particular cellular and/or biochemical processes. With this respect, cultured cells offer the possibility to study the presence of binding sites in conjunction with ligand induced signaling. This link is discussed for the AT4 receptor by providing an overview of the cellular effects by AT4 ligands. 相似文献
103.
N. Inguimbert P. Coric H. Dhotel E. Bonnard C. Llorens‐Cortes N. De Mota M.‐C. Fourni‐Zaluski B.‐P. Roques 《Chemical biology & drug design》2005,65(2):175-188
Abstract: Aminopeptidase A (APA) is involved in the maturation of angiotensin III, a peptide which seems to be implicated in blood pressure regulation at the brain level. Therefore APA inhibitors are potential new antihypertensive agents with possible novel applications. With the aim of enhancing the bioavailability and potency of EC 33, the APA inhibitor (Ki = 300 nm ) initially used in the earlier studies, we have synthesized new non‐peptidic inhibitors able to interact with the S1 and S subsites of the targeted enzyme. Compound 10a , (3S,4S)‐3‐amino‐4‐mercapto‐6‐phenyl‐hexane‐1‐sulfonic acid was obtained using an asymmetric synthesis. Inhibitor 10a exhibits a Ki value of 30 nm . 相似文献
104.
Aminopeptidase N is involved in cell motility and angiogenesis: its clinical significance in human colon cancer 总被引:6,自引:0,他引:6
Hashida H Takabayashi A Kanai M Adachi M Kondo K Kohno N Yamaoka Y Miyake M 《Gastroenterology》2002,122(2):376-386
BACKGROUND & AIMS: The molecular basis of cell motility is highly complex and is controlled by a number of molecular systems, whereas angiogenesis is an important biological component of tumor progression. The aims of this study were to investigate the possible involvement of proteins at the cell surface in controlling cell motility and angiogenesis, and to identify the cell surface molecules involved in gastrointestinal tumors. METHODS: We addressed these issues using functional monoclonal antibodies, which inhibit cell motility, endothelial cell migration, and tube formation. Furthermore, we investigated the relationship between this antigen and colon cancer, and showed the prognostic significance in human colon cancer. RESULTS: We established a murine monoclonal antibody MH8-11, which inhibits cell motility and in vitro angiogenesis. This epitope was a 165-kilodalton protein, and the sequencing analysis revealed that it was almost identical to aminopeptidase N (APN)/cluster of differentiation (CD) 13. APN/CD13 expression was associated with tumor status (P = 0.025). The disease-free and overall survival rate for patients with positive APN/CD13 expression tumors was significantly lower than that for patients with negative APN/CD13 expression tumors (P = 0.014, 0.033, respectively). Among 47 node-positive patients, the survival rate of patients with negative APN/CD13 expression was better than that of those with positive APN/CD13 expression. CONCLUSIONS: Our data suggest that APN/CD13 is involved in cell motility and angiogenesis, and APN/CD13 expression may be a useful indicator of a poor prognosis for node-positive patients with colon cancer. 相似文献
105.
Human melanoma invasion and metastasis enhancement by high expression of aminopeptidase N/CD13 总被引:4,自引:0,他引:4
Hideji Fujii Motowo Nakajima Ikuo Saiki Junya Yoneda Ichiro Azuma Takashi Tsuruo 《Clinical & experimental metastasis》1995,13(5):337-344
Aminopeptidase N/CD13 is a Zn2+-dependent exoprotease present on the cell surface as a transmembrane protein. Our previous studies using aminopeptidase inhibitors and antibodies demonstrated that aminopeptidase N is involved in the degradation and invasion of the extracellular matrix (ECM) by metastatic tumor cells. In the present study we transfected human A375M melanoma cells with eukaryotic plasmid expression vectors that contained full length cDNA of aminopeptidase N/CD13 and examined their characteristics. The transfectants that expressed extremely high levels of aminopeptidase N/CD13 degraded type IV collagen and invaded ECM more actively than the parental and control vector-transfected cells. Furthermore, the aminopeptidase N/CD13-transfected A375M cells had significantly augmented lung colonizing potential in nude mice. The results show that the aminopeptidase N/CD13 plays an active role in degradation and invasion of ECM and may be involved in the molecular mechanisms of blood-borne metastasis. 相似文献
106.
107.
目的研究白细胞源性精氨酸氨基肽酶(Leukocyte-derived Arginine Aminopeptidase,L-Rap)在高糖培养的人视网膜血管内皮细胞的表达,分析L-Rap蛋白的功能。方法体外培养人视网膜血管内皮细胞,实时定量PCR检测L-Rap在高糖培养的人视网膜血管内皮细胞的表达变化,建立L-Rap的三维蛋白结构图,分析L-Rap蛋白的功能。结果L-Rap的mRNA在高糖培养的人视网膜血管内皮细胞下降,L-Rap蛋白可能对血管生成因子、免疫炎症因子以及肾素-血管紧张素系统发挥作用。结论L-Rap与糖尿病视网膜病变密切相关,可以从血管生成因子、免疫炎症因子以及肾素-血管紧张素系统这三个途径探索L-Rap对糖尿病视网膜病变的作用。 相似文献
108.
109.
Effect of tuftsin on leucyl aminopeptidase activity of subcellular components of the cerebral cortex
A. S. Kamysheva 《Bulletin of experimental biology and medicine》1989,107(2):223-225
Laboratory of Cytochemistry, Brain Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. S. Adrianov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 107, No. 2, pp. 209–211, February, 1989. 相似文献
110.