Synthesis and mass-spectrometric characterization of human serum albumins modified by covalent binding of two non-steroidal anti-inflammatory drugs: tolmetin and zomepirac.
Synthesis and mass-spectrometric characterization of human serum albumins modified by covalent binding of two non-steroidal anti-inflammatory drugs: tolmetin and zomepirac.
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通过两种非甾体抗炎药托美丁和佐美拉共价结合修饰的人血清白蛋白的合成和质谱表征。
DOI：
10.1042/bj3110431
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Benet,LZ
中科院分区：
文献类型：
--
作者：
Zia-Amirhosseini,P;Ding,A;Burlingame,AL;McDonagh,AF;Benet,LZ
合成了共价结合托美丁或佐美酸修饰的人血清白蛋白，作为酰基葡萄糖醛酸在体内形成的类似产物的模型。用1-乙基-3-（3-二甲氨基丙基）-N-酰亚胺制备两种药物的活化酯，然后使其与人血清白蛋白反应。通过HPLC分析两种蛋白质产物的胰蛋白酶底物，以鉴定含有共价结合药物的肽，并通过高效串联MS鉴定白蛋白上的结合位点。两种产物共有三个结合位点，即赖氨酸-195、-199和-351。对于托美汀-白蛋白产物，鉴定了三个进一步修饰的残基，即天冬氨酸1和赖氨酸-524和-536。
Human serum albumins modified by covalently bound tolmetin or zomepirac were synthesized as models for similar products formed in vivo from acyl glucuronides. Activated esters of both drugs were prepared with 1-ethyl-3-(3-dimethylaminopropyl)-carbodi-imide, and then allowed to react with human serum albumin. Tryptic digests of both protein products were analysed by HPLC to identify peptides containing covalently bound drugs, and binding sites on albumin were identified by high-performance tandem MS. Three binding sites were common to both products, i.e. lysine-195, -199 and -351. Three further modified residues were identified for the tolmetin-albumin product, i.e. aspartic acid 1, and lysine-524 and -536.