title: "Switch off/switch on" regulation of drug cytotoxicity by conjugation to a cell targeting peptide.
abstract: 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).
authors.affiliation: Department of Biological Chemistry, Ariel University, Ariel, 40700, Israel; The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar Ilan University, Ramat Gan, 52900, Israel.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Gilad
authors.affiliation: Department of Chemical Engineering, Ariel University, Ariel, 40700, Israel.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Firer
authors.affiliation: Department of Biological Chemistry, Ariel University, Ariel, 40700, Israel; The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar Ilan University, Ramat Gan, 52900, Israel.
authors.forename: Alex
authors.initials: A
authors.lastname: Rozovsky
authors.affiliation: Department of Biological Chemistry, Ariel University, Ariel, 40700, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Ragozin
authors.affiliation: Department of Biological Chemistry, Ariel University, Ariel, 40700, Israel; The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar Ilan University, Ramat Gan, 52900, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Redko
authors.affiliation: The Julius Spokojny Bioorganic Chemistry Laboratory, Department of Chemistry, Bar Ilan University, Ramat Gan, 52900, Israel.
authors.forename: Amnon
authors.initials: A
authors.lastname: Albeck
authors.affiliation: Department of Biological Chemistry, Ariel University, Ariel, 40700, Israel. Electronic address: garyg@ariel.ac.il.
authors.forename: Gary
authors.initials: G
authors.lastname: Gellerman
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D004337:Drug Carriers
keywords: Amino acid platform; Controlled drug release; Peptide–drug conjugates; Prodrug; Solid phase organic synthesis