Linkage of boronated polylysine to glycoside moieties of polyclonal antibody; boronated antibodies as potential delivery agents for neutron capture therapy

被引:11
作者
Novick, S
Quastel, MR [1 ]
Marcus, S
Chipman, D
Shani, G
Barth, RF
Soloway, AH
机构
[1] Ben Gurion Univ Negev, Soroka Med Ctr, Inst Nucl Med, IL-84105 Beer Sheva, Israel
[2] Ben Gurion Univ Negev, Soroka Med Ctr, Fac Life Sci, IL-84105 Beer Sheva, Israel
[3] Ben Gurion Univ Negev, Soroka Med Ctr, Dept Nucl Engn, IL-84105 Beer Sheva, Israel
[4] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA
[5] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA
关键词
boron; polylysine; boronation; immunoreactivity; BNCT; neutron capture; antibody; boronated antibody;
D O I
10.1016/S0969-8051(01)00297-9
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Among the ways to deliver comparatively large amounts of boron to cells in vitro for boron neutron capture studies is the linkage of a boronated macromolecule such as polylysine to an antibody. In order to reduce interference with immunoreactivity, boronated polylysine (BPL) was linked to oligosaccharide moieties on the IgG molecule distant from the antibody combining sites. The resultant bioconjugate was chromatographically separated from free BPL and unconjugated antibody using a Sephacryl S300 column. The total measured boron per BPL-IgG conjugate, determined by direct current plasma atomic emission spectroscopy, was estimated to be similar to6 x 10(3) atoms. This, together with molecular weight estimations, indicated conjugation of about 3 polylysines to each IgG molecule. Immunoreactivity of the conjugate was found to be the same as that of the unconjugated polyclonal antibody. This was based on its concentration dependent interference with immunometric reactions for an antigen (TSH), whereas heat inactivated or non-specific antibody had no such inhibitory effects. The results support the hypothesis that the binding affinity of the conjugate for antigen was preserved after its linkage to BPL under the conditions described. The methodology described in this report may have applicability for the preparation of boronated antibodies as delivery agents for BNCT. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:159 / 167
页数:9
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