The Florida State University Research Foundation, Inc.

Serguei V Kovalenko

Igor Alabugin

Boris Breiner

Joerg C Schlatterer

Nancy L Greenbaum

Kerry Gilmore

Wang Yong Yang

Compounds and methods for double-stranded DNA cleavage of light-activated lysine conjugates are enhanced at the slightly acidic pH suitable for selective targeting of cancer cells by the presence of two amino groups of different basicities. The first amino group plays an auxiliary role enhancing solubility and affinity to DNA whereas the second amino group which is positioned next to the light-activated DNA-cleaver undergoes protonation at the desired pH threshold. Protonation results in two synergetic effects which account for the increased DNA-cleaving ability at the lower pH: tighter binding to DNA at the lower pH; and the unproductive pathway which quenches the excited state of the photocleaver through intramolecular electron transfer is eliminated once the donor amino group next to the chromophore is protonated. The utility of these molecules for phototherapy of cancer is confirmed by the drastic increase in toxicity of five conjugates against cancer cell lines upon photoactivation.

C-lysine conjugates as pH-controlled, light-activated reagents for double stranded DNA cleavage and associated methods

A process of forming a double strand cleavage in DNA includes providing a reaction mixture containing double stranded DNA having a break in a first strand defining a target site in a second strand. The method continues by adding to the reaction mixture a photoreactive lysine conjugate selected from a lysine-enediyne conjugate, a lysine-acetylene conjugate or a combination thereof, for a time sufficient for the lysine conjugate to bind to the DNA adjacent the target site. The reaction mixture is then irradiated with electromagnetic radiation sufficient to photoactivate the lysine conjugate to cleave the second strand adjacent the target site.

Site-specific cleavage of nucleic acids by photoreactive conjugates

Growing community of inventors

Tallahassee, FL, United States of America

Serguei V Kovalenko