title: Optimizing Protonation States for Selective Double-Strand DNA Photocleavage in Hypoxic Tumors: pH-Gated Transitions of Lysine Dipeptides.
abstract: We report pH-switching properties of the new family of dipeptide-acetylene conjugates where pH-gated light-activated double-strand (ds) DNA cleavage is controlled by variations in electronic and geometric parameters. The conjugates have higher activities at the slightly acidic pH values that separate normal and cancerous tissue (pH < 7). This favorable pH dependence originates from several elements of structural design. Basicities of the two amines determine the threshold pH range where the changes in binding and reactivity are observed, whereas the distance between the two amino groups and the hydrophobic aryl alkyne moiety can further modulate DNA binding. The changes of the protonation state from a neutral molecule to a dication results in dramatically increased efficiency of ds DNA photocleavage, the most therapeutically valuable type of DNA cleavage.
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306-4390, United States.|Department of Chemistry, Dumlupınar University , Kütahya, 43100 Turkey.
authors.forename: Kemal
authors.initials: K
authors.lastname: Kaya
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306-4390, United States.
authors.forename: Saumya
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306-4390, United States.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Nogues
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306-4390, United States.
authors.forename: Juan Camilo
authors.initials: JC
authors.lastname: Rojas
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306-4390, United States.
authors.forename: Zlatko
authors.initials: Z
authors.lastname: Sokolikj
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University , Tallahassee, Florida 32306, United States.
authors.forename: Diego A R
authors.initials: DA
authors.lastname: Zorio
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University , Tallahassee, Florida 32306-4390, United States.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Alabugin
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D008239:Lysine / Q000737:chemistry / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy; D010782:Photolysis / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011522:Protons
chemical_list: D004151:Dipeptides; D017319:Photosensitizing Agents; D011522:Protons; D004247:DNA; D008239:Lysine; D000114:Acetylene