Beta-lactam-based approach for the chemical programming of aldolase antibody 38C2.
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(v)beta(3) and alpha(v)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.
Gavrilyuk
Julia I
JI
The Skaggs Institute for Chemical Biology and the Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Wuellner
Ulrich
U
Barbas
Carlos F
CF
D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005634:Fructose-Bisphosphate Aldolase / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000378:metabolism
D017151:Antibodies, Catalytic; D007140:Immunoglobulin Fab Fragments; D047090:beta-Lactams; C109536:antibody aldolase; D005634:Fructose-Bisphosphate Aldolase