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

Yossi Gilad; Michael A. Firer; Alex Rozovsky; Elena Ragozin; Boris Redko; Amnon Albeck; Gary Gellerman

doi:10.1016/j.ejmech.2014.07.073

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

Yossi Gilad, Michael A. Firer, Alex Rozovsky, Elena Ragozin, Boris Redko, Amnon Albeck, Gary Gellerman

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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).

Original language	English
Pages (from-to)	139-146
Number of pages	8
Journal	European Journal of Medicinal Chemistry
Volume	85
DOIs	https://doi.org/10.1016/j.ejmech.2014.07.073
State	Published - 6 Oct 2014

Keywords

Amino acid platform
Controlled drug release
Peptide-drug conjugates
Prodrug
Solid phase organic synthesis

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10.1016/j.ejmech.2014.07.073

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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).",

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T1 - "Switch off/switch on" regulation of drug cytotoxicity by conjugation to a cell targeting peptide

AU - Gilad, Yossi

AU - Firer, Michael A.

AU - Rozovsky, Alex

AU - Ragozin, Elena

AU - Redko, Boris

AU - Albeck, Amnon

AU - Gellerman, Gary

PY - 2014/10/6

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AB - 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).

KW - Amino acid platform

KW - Controlled drug release

KW - Peptide-drug conjugates

KW - Prodrug

KW - Solid phase organic synthesis

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

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