Targeted delivery of cytotoxins represents the frontier of cancer therapy in which antibody-drug conjugates (ADCs) are utilized to deliver organic toxins. Platinum compounds are the most commonly utilized cytotoxins, but a viable conjugate system has not yet been developed.  We generated an approach for targeted delivery of platinum to cancer cells by including a tripeptide carrier inline with a targeting protein and inserting metal via a novel reaction. Platinum binding to our carrier is irreversible at physiological pH; the complex is extraordinarily stable, but the metal is released upon acidification, permitting controlled release.  Our unique system provides the ability to rationally design and site-specifically encode the tripeptide into desired positions within a protein, generating a homogeneous product, which can be well-characterized. Metal-containing conjugates pose different challenges for assessment of the protein product and its overall stability.  Here we describe development and characterization of our metal-carrier system.

Characterization of platinum-protein conjugates for targeted anti-cancer therapy

243rd National Meeting (2012)

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