title: Hybrids of amino acids and acetylenic DNA-photocleavers: optimising efficiency and selectivity for cancer phototherapy.
abstract: Hybrid agents which combine potent DNA-photocleavers with tunable amino acids or small peptides were designed to improve selectivity of Nature's most potent class of antibiotics towards cancer cells. The ability of these compounds to photocleave DNA is controlled by their incorporation into hybrid architectures with functional elements derived from natural amino acids. These conjugates are highly effective at inducing double-strand DNA cleavage and, in some cases, rival or even surpass both naturally occurring DNA cleavers and anticancer agents that are currently in clinical use. The possibility of triggering their activity in a photochemical and pH-sensitive fashion allows for a high degree of selectivity over activation. The conjugates were shown to penetrate cell membranes and induce efficient intracellular DNA cleavage. Initial in vitro tests against a variety of cancer cell lines confirm the potential of these compounds as anticancer agents at low nanomolar concentrations.
authors.affiliation: Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Breiner
authors.forename: Kemal
authors.initials: K
authors.lastname: Kaya
authors.forename: Saumya
authors.initials: S
authors.lastname: Roy
authors.forename: Wang-Yong
authors.initials: WY
authors.lastname: Yang
authors.forename: Igor V
authors.initials: IV
authors.lastname: Alabugin
mesh_terms: D000107:Acetylation; D000596:Amino Acids / Q000737:chemistry*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003500:Cyclization; D004247:DNA / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000737:chemistry* / Q000473:pathology; D055668:Photochemical Processes
chemical_list: D000596:Amino Acids; D004247:DNA