“Switch off/switch on” regulation of drug cytotoxicity by conjugation to a cell targeting peptide

•Amino-acid platforms loaded with various two different drugs were synthesized.•They were synthesized by fast SPOC, accelerating discovery process.•They possess a linkage tether for conjugation to a peptide carrier.•They provide discrete chemo- and bio-release profiles for each drug.•They enable “switch off/switch on” regulation of cytotoxicity by cell targeting.

Bi-nuclear amino acid platforms loaded with various drugs for conjugation to a peptide carrier were synthesized using simple and convenient orthogonally protective solid-phase organic synthesis (SPOS). Each arm of the platform carries a different anticancer agent linked through the same or different functional group, providing discrete chemo- and bio-release profiles for each drug, and also enabling “switch off/switch on” regulation of drug cytotoxicity by conjugation to the platform and to a cell targeting peptide. The versatility of this approach enables efficient production of drug-loaded platforms and determination of favorable drug combinations/modes of linkage for subsequent conjugation to a carrier moiety for targeted cancer cell therapy. The results presented here potentiate the application of amino acid platforms for targeted drug delivery (TDD).

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