Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates targeted to the B-cell antigen CD20.
Synthesis and evaluation of multivalent branched HPMA copolymer-Fab' conjugates targeted to the B-cell antigen CD20.
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DOI：
10.1021/bc800351m
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发表时间：
2009-01
影响因子：
4.7
通讯作者：
Kopecek J
中科院分区：
文献类型：
--
作者：
Johnson RN;Kopecková P;Kopecek J
几种药物递送设计将联合收割机合成药物载体与共价缀合的靶向部分组合。单克隆抗体（mAb）或其Fab′片段的此类修饰不可避免地导致其对靶组织的亲和力降低。为了克服这一限制，合成了高分子量、支化N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物，并与抗CD 20抗体1F 5的Fab '片段缀合。这产生了靶向B细胞抗原CD 20的具有不同化合价（每个大分子的Fab '的量）的多价缀合物。通过测定低浓度偶联物的表观KD、Sips异质性因子α和各构建体的结合增强因子来评价多价效应。结果表明，多价性可提高HPMA共聚物-Fab ′结合物与未结合mAb的亲和力。
Several drug delivery designs combine synthetic drug carriers with covalently conjugated targeting moieties. Such modifications of monoclonal antibodies (mAb), or their Fab′ fragments, inevitably result in diminished affinity for their targeted tissue. In an attempt to overcome this limitation, high molecular weight, branched N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesized and conjugated with Fab′ fragments of the anti-CD20 antibody, 1F5. This produced multivalent conjugates with varying valency (amount of Fab′ per macromolecule) targeted to the B-cell antigen CD20. Evaluation of a multivalent effect was done by determining the apparent KD at low concentrations of conjugates, the Sips heterogeneity factor, a, and the binding enhancement factors of each construct. The results clearly indicated that multivalency could improve the affinity of the HPMA copolymer–Fab′ conjugates to that of unconjugated mAb.
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影响因子：
10.8
作者：
CARTLIDGE S A;DUCAN R;KOPECEK J
通讯作者：
KOPECEK J
影响因子：
4.7
作者：
Ding, H;Prodinger, WM;Kopecek, J
通讯作者：
Kopecek, J
影响因子：
3.4
作者：
ALLEN, TM;BRANDEIS, E;ZALIPSKY, S
通讯作者：
ZALIPSKY, S
影响因子：
3.6
作者：
DELISI, C
通讯作者：
DELISI, C
影响因子：
10.8
作者：
Dvorák, M;Kopecková, P;Kopecek, J
通讯作者：
Kopecek, J