Steven F, Griffin M M, Williams L A, Feichter G
Department of Biochemistry and Molecular Biology, School of Biological Sciences, University of Manchester, England.
Anticancer Res. 1988 Nov-Dec;8(6):1179-83.
We have employed ethanol-fixed wax embedded sections of human breast tumours and smears of rat leukaemia cells to provide test systems with recognisable tumour cells amongst normal cells. We have used 9-aminoacridine to locate cells possesing guanidinobenzoatase, an enzyme which degrades fibronectin and which binds 9-aminoacridine to its active centre. The binding of 9-aminoacridine to tumour cells allows these cells to be located by fluorescent microscopy. Pre-treatment of these sections with BZAR, a known inhibitor of guanidinobenzoatase inhibited the binding of 9-aminoacridine to the tumour cells. These techniques defined the tumour cells in the sections; we then demonstrated by fluorescent microscopy that both Texas red-agmatine and BZAR also bound to the guanidinobenzoatase of these tumour cells. These fluorescent probes have been used as model compounds to illustrate the ability of both N-substituted agmatines and N-substituted arginines to deliver desired molecules to an enzyme on the surface of tumour cells. Replacement of these fluorescent moieties by cytotoxic moieties attached to the same ligands could lead to selective drug delivery to tumour cells.
我们采用了人乳腺肿瘤的乙醇固定石蜡包埋切片以及大鼠白血病细胞涂片，以提供在正常细胞中含有可识别肿瘤细胞的测试系统。我们使用9-氨基吖啶来定位具有胍基苯甲酸酶的细胞，该酶可降解纤连蛋白并将9-氨基吖啶结合至其活性中心。9-氨基吖啶与肿瘤细胞的结合使得这些细胞能够通过荧光显微镜进行定位。用已知的胍基苯甲酸酶抑制剂BZAR对这些切片进行预处理，可抑制9-氨基吖啶与肿瘤细胞的结合。这些技术确定了切片中的肿瘤细胞；然后我们通过荧光显微镜证明，德克萨斯红-胍丁胺和BZAR也与这些肿瘤细胞的胍基苯甲酸酶结合。这些荧光探针已被用作模型化合物，以说明N-取代胍丁胺和N-取代精氨酸将所需分子递送至肿瘤细胞表面酶的能力。用连接到相同配体上的细胞毒性部分取代这些荧光部分可能导致向肿瘤细胞的选择性药物递送。
