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.

Florida State University Research Foundation, Inc.

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

This invention concerns a coordination complex and salts and optically resolved enantiomers thereof, of the formula (R).sub.3 --M, wherein R comprises 1,10-phenanthroline or a substituted derivative thereof, M comprises a suitable transition metal, e.g. ruthenium(II), RHODIUM(III) or cobalt(III), and R is bonded to M by a coordination bond.The complexes of this invention are useful in methods for labeling, nicking and cleaving DNA. The lambda enantiomer of complexes of this invention is useful in methods for specifically labeling, detecting, nicking and cleaving Z-DNA or A-DNA.The complexes may also be used in a method for killing tumor cells and may be combined with a pharmaceutically acceptable carrier to form a pharmaceutical composition for the treatment of tumor cells in a subject. The invention further concerns methods for treating a subject affilicted with tumor cells.

The Trustees of Columbia University In The City of New York

galium verum/syöpä

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

Chemical probes for left-handed DNA and for A-DNA; chiral metal complexes as Z-specific antitumor agents and as double strand cleavers

Täydellisin lääketieteellinen tietokanta tieteen tukemana