Antibody drug conjugates (ADCs) have been developed to deliver organic cytotoxins, but a conjugate approach for therapeutic delivery of platinum (Pt) remains needed. Platinum poses unique challenges for both synthesis and stability of protein conjugates. We are developing our peptide-based metal carrier to achieve targeted delivery of platinum. The Pt-peptide (Asn-Cys-Cys) is compatible with either inline incorporation into a protein or chemical linking approaches. The chemistries used to link peptides to antibodies can yield products susceptible to side reactions, particularly peptides containing cysteine residues. Optimization of reaction chemistry and incorporation of platinum are necessary to maximize yield and stability of the desired product. Introduction of free thiols on the protein surface can lead to crosslinking; because platinum incorporation quenches thiol reactivity, efficient metal binding is crucial for protein stability. Here we present approaches to efficiently conjugate cysteine-containing peptides to antibodies and incorporate platinum, generating conjugates for targeted anti-cancer therapy.

Covalent modification of monoclonal antibodies with thiol-containing peptides for targeted platinum delivery

245th National Meeting (2013)

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