iBodies: Modular Synthetic Antibody Mimetics Based on Hydrophilic Polymers Decorated with Functional Moieties

被引:33
|
作者
Sacha, Pavel [1 ,3 ]
Knedlik, Tomas [1 ,3 ]
Schimer, Jiri [1 ,3 ]
Tykvart, Jan [1 ,3 ]
Parolek, Jan [1 ,3 ]
Navratil, Vaclav [1 ,3 ]
Dvorakova, Petra [1 ]
Sedlak, Frantisek [1 ,4 ]
Ulbrich, Karel [2 ]
Strohalm, Jiri [2 ]
Majer, Pavel [1 ]
Subr, Vladimir [2 ]
Konvalinka, Jan [1 ,3 ]
机构
[1] Acad Sci Czech Republic, Inst Organ Chem & Biochem, Flemingovo 2, Prague 16610 6, Czech Republic
[2] Acad Sci Czech Republic, Inst Macromol Chem, Heyrovskeho 2, Prague 16206 6, Czech Republic
[3] Charles Univ Prague, Fac Sci, Dept Biochem, Hlavova 8, Prague 12843 2, Czech Republic
[4] Charles Univ Prague, Fac Med 1, Katerinsk 32, Prague 12108 2, Czech Republic
关键词
antibody mimetics; HPMA; molecular recognition; polymer conjugates; protein targeting; GLUTAMATE CARBOXYPEPTIDASE II; MEMBRANE ANTIGEN; COMBINATORIAL LIBRARIES; MOLECULES; PROTEINS; DOMAIN;
D O I
10.1002/anie.201508642
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Antibodies are indispensable tools for biomedicine and anticancer therapy. Nevertheless, their use is compromised by high production costs, limited stability, and difficulty of chemical modification. The design and preparation of synthetic polymer conjugates capable of replacing antibodies in biomedical applications such as ELISA, flow cytometry, immunocytochemistry, and immunoprecipitation is reported. The conjugates, named " iBodies", consist of an HPMA copolymer decorated with low-molecular-weight compounds that function as targeting ligands, affinity anchors, and imaging probes. We prepared specific conjugates targeting several proteins with known ligands and used these iBodies for enzyme inhibition, protein isolation, immobilization, quantification, and live-cell imaging. Our data indicate that this highly modular and versatile polymer system can be used to produce inexpensive and stable antibody substitutes directed toward virtually any protein of interest with a known ligand.
引用
收藏
页码:2356 / 2360
页数:5
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