Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 139, Issue 36, Pages 12617-12622Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.7b06428
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Funding
- NSF [CHE-1609654, CHE-1055569]
- Robert A. Welch Foundation research grant [C-1680]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1609654] Funding Source: National Science Foundation
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Preparation of antibody drug conjugates (ADCs), an emerging novel class of highly targeted biological hybrid agents, necessitates precise control of conjugation reactivity. Antibodies have complex multistranded architectures, and specific modification of natural antibodies has proven quite challenging. Here, we demonstrate that cooperative activity of a multimetallic metallopeptide enables efficient site-specific antibody functionalization, based on molecular recognition of the constant Fc region. This interplay of multiple metal centers enables introduction of an orthogonal alkyne handle into monoclonal or polydonal antibodies from different species in an Fc-specific fashion. Elaboration of this simple functionalization allows preparation of conjugates with fluorophore, affinity handle, and pharmacological agents. This method opens a new opportunity for quick and easy production of well-defined antibody conjugates from a variety of antibody sequence and species of origin.
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