Abstract
Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with β-lactam-equipped targeting modules. A model study was first performed with β-lactam conjugated to biotin. This conjugate efficiently and selectively modified the catalytic site lysine (LysH93) of mAb 38C2. We then conjugated a β-lactam to a cyclic-RGD peptide to chemically program mAb 38C2 to target integrin receptors α vβ 3 and α vβ 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.
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