Multiple catalytic aldolase antibodies suitable for chemical programming.
Chemical programming of nine murine antibodies with catalytic aldolase activity was examined using compounds, equipped with diketone or pro-vinyl ketone linkers that inhibit integrin adhesion receptor functions. The results showed that most Abs were programmed using the diketone compounds in a manner similar to previously reported catalytic antibody 38C2. On the other hand, only those antibodies, which catalyzed the retro aldol reaction of the pro-vinyl ketone linkers efficiently, were programmed. Conjugated to integrin targeting compounds, at least three new antibodies, including 84G3, 85H6, and 90G8, exhibited high specific binding to human tumor cells expressing integrin alpha(v)beta(3.).
The Skaggs Institute for Chemical Biology, Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Rajib Kumar
RK
Goswami
Zheng-Zheng
ZZ
Huang
Jane S
JS
Forsyth
Brunhilde
B
Felding-Habermann
Subhash C
SC
Sinha
D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007659:Ketones / Q000737:chemistry
D017151:Antibodies, Catalytic; D007140:Immunoglobulin Fab Fragments; D039302:Integrin alphaVbeta3; D007659:Ketones; C109536:antibody aldolase; D005634:Fructose-Bisphosphate Aldolase