β-Lactam-based approach for the chemical programming of aldolase antibody 38C2

被引：34

作者：

Gavrilyuk, Julia I.

Wuellner, Ulrich

Barbas, Carlos F., III ^{[1
]}

机构：

[1] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Monoclonal antibody; Aldolase antibody; Chemically programmed antibody; Integrins; CLICK CHEMISTRY; ADAPTER IMMUNOTHERAPY; CATALYTIC ANTIBODIES; MOLECULES; AZIDES;

D O I：

10.1016/j.bmcl.2009.01.028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with beta-lactam-equipped targeting modules. A model study was first performed with beta-lactam conjugated to biotin. This conjugate efficiently and selectively modified the catalytic site lysine (LysH93) of mAb 38C2. We then conjugated a beta-lactam to a cyclic-RGD peptide to chemically program mAb 38C2 to target integrin receptors alpha(nu)beta(3) and alpha(nu)beta(5). The chemically programmed antibody bound specifically to the isolated integrin receptor proteins as well as the integrins expressed on human melanoma cells. This approach provides an efficient and versatile solution to irreversible chemical programming of aldolase antibodies. (C) 2009 Elsevier Ltd. All rights reserved.

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页码：1421 / 1424

页数：4

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