Lu Z R, Gao S Q, Kopecková P, Kopecek J
Departments of Pharmaceutics and Pharmaceutical Chemistry/CCCD, and Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.
Bioconjug Chem. 2000 Jan-Feb;11(1):3-7. doi: 10.1021/bc990098a.
An amino group containing cyclosporin A (CsA) derivative has been synthesized and conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via an aromatic azo bond, which can be specifically cleaved by azoreductase activity in colon to release the drug for the treatment of colon diseases. Lectins, peanut (Arachis hypogea) agglutinin (PNA) and wheat germ agglutinin (WGA), have been conjugated to HPMA copolymer-CsA derivative conjugates (PCsA), respectively, to give bioadhesive conjugates. The PNA and WGA are the targeting proteins that can bind to diseased colon tissue and healthy tissue, respectively. There were on average four P(CsA) copolymer chains attached on one WGA molecule with a drug content of 16.0 wt % and five P(CsA) copolymer chains attached on one PNA molecule with a drug content of 11.5 wt %. The incubation of a P(CsA) copolymer with the rat cecal contents resulted in the cleavage of the azo bond and release of the cyclosporin derivative. The biological evaluation of the conjugates is under way.
一种含氨基的环孢素A（CsA）衍生物已被合成，并通过芳香偶氮键与N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物缀合，该偶氮键可在结肠中被偶氮还原酶活性特异性裂解以释放药物用于治疗结肠疾病。凝集素，花生（Arachis hypogea）凝集素（PNA）和麦胚凝集素（WGA），已分别与HPMA共聚物-CsA衍生物缀合物（PCsA）缀合，得到生物粘附缀合物。PNA和WGA分别是可与病变结肠组织和健康组织结合的靶向蛋白。平均一个WGA分子上连接有四条P（CsA）共聚物链，药物含量为16.0 wt%，一个PNA分子上连接有五条P（CsA）共聚物链，药物含量为11.5 wt%。P（CsA）共聚物与大鼠盲肠内容物孵育导致偶氮键裂解并释放环孢素衍生物。缀合物的生物学评价正在进行中。
