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Synthesis of Glutathione (GSH)-Responsive Amphiphilic Duplexes and their Application in Gene Delivery.

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Oligoamide molecular strands with hydrogen-bonding sequences DADDAD and guanidine (O-1) or 1,5,9-triazacyclododecane ([12]aneN3 ; O-2) side chains and oligoamides with hydrogen-bonding sequences ADAADA and octyl moieties (O-3), were synthesized. Two… Click to show full abstract

Oligoamide molecular strands with hydrogen-bonding sequences DADDAD and guanidine (O-1) or 1,5,9-triazacyclododecane ([12]aneN3 ; O-2) side chains and oligoamides with hydrogen-bonding sequences ADAADA and octyl moieties (O-3), were synthesized. Two duplexes (D-1 and D-2) were prepared by conjugating the hydrophilic O-1 or O-2 and hydrophobic O-3 through sequence-specific hydrogen-bond association and cross-linked disulfide bonds. Electrophoresis measurements indicated that O-1, O-2, D-1, and D-2 were able to completely retard the DNA mobiliy at concentrations of 30, 30, 10, and 20 μM, respectively. Reversible DNA release in O-1 and O-2 complexes can be achieved in the presence of heparin sodium, whereas the presence of GSH greatly improved DNA release in D-1 and D-2 complexes. The particles formed were in a size range of 50-170 nm with positively charged surfaces. D-1 and D-2 transfected pEGFP-N1 into HeLa cells successfully.

Keywords: synthesis glutathione; glutathione gsh; gsh responsive; responsive amphiphilic; gsh; amphiphilic duplexes

Journal Title: ChemPlusChem
Year Published: 2019

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