课题基金 / 基金详情

"STRUCTURE-FUNCTION STUDIES OF DIHYDROFOLATE REDUCTASE"

"STRUCTURE-FUNCTION STUDIES OF DIHYDROFOLATE REDUCTASE"
“二氢叶酸还原酶的结构功能研究”
批准号:
3181953
负责人:
JAMES H. FREISHEIM
金额:
$17.14万
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-05-01 至 1988-04-30

项目摘要

项目成果

JAMES H. FREISHEIM的其他基金

相似基金

相关文献

中文摘要
翻译
这个项目关注的是结构与 二氢叶酸还原酶(二氢叶酸+NADPH+H+-)的功能 四氢叶酸+NADP+)。使用多种蛋白质技术 化学方面,要研究的问题包括:(A)获取蛋白质 甲氨蝶呤(MTX)不敏感酶的序列信息 MTX耐药的L5178Y细胞和Walker 256癌肉瘤细胞 主要通过衍生多肽的高效液相色谱图谱和氨基酸分析;(B) 蛋白质的特定氨基酸残基的化学修饰和 测量这些修饰对衬底的影响, 辅因子和抑制剂结合及对酶活性的影响;(C)平衡 底物、辅因子和抑制剂结合作用的研究 人、L5178Y和Walker 256细胞,采用荧光技术,圆形 二向色性和平衡透析技术;(D)甲氨蝶呤的评价 作为二氢叶酸还原酶亲和标记和光亲和标记的类似物; (E)检查选定的、取代的喹唑啉、三氮唑类和 酶抑制剂的蝶呤类药物及其转运的测定 甲氨蝶呤敏感和耐药细胞的特征。
英文摘要
This project is concerned with the relation of the structure to the function of dihydrofolate reductase (dihydrofolate+ NADPH + H+ - tetrahydrofolate + NADP+). Using a number of techniques of protein chemistry, the problems to be investigated include: (a) obtaining protein sequence information on a methotrexate (MTX)-insensitive enzyme from MTX-resistant L5178Y cells and from Walker 256 carcinosarcoma cells primarily by HPLC-mapping of derived peptides and amino acid analysis; (b) chemical modification of specific amino acid residues of the protein and measurements of the effect of these modifications on the substrate, cofactor and inhibitor binding and on enzymic activity; (c) equilibrium binding studies of substrate, cofactor and inhibitors using reductases from human, L5178Y and Walker 256 cells and employing fluorescence, circular dichroism and equilibrium dialysis techniques; (d) evaluation of MTX analogues as affinity and photoaffinity labels of dihydrofolate reductases; (e) examination of selected, substituted quinazolines, triazines and pteridines as enzyme inhibitors and a determination of their transport characteristics in MTX-sensitive and -resistant cells.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
"STRUCTURE-FUNCTION STUDIES OF DIHYDROFOLATE REDUCTASE"
STRUCTURE-FUNCTION STUDIES OF DIHYDROFOLATE REDUCTASE
STRUCTURE-FUNCTION STUDIES OF DIHYDROFOLATE REDUCTASE
"STRUCTURE-FUNCTION STUDIES OF DIHYDROFOLATE REDUCTASE"
海外基金