PNA-Rose Bengal Conjugates as Efficient DNA Photomodulators.
Selective photoinduced modulation of DNA may provide a powerful therapeutic tool allowing spatial and temporal control of the photochemical reaction. We have explored the photoreactivity of peptide nucleic acid (PNA) conjugates that were conjugated to a highly potent photosensitizer, Rose Bengal (RB). In addition, a short PEGylated peptide (K-PEG8-K) was conjugated to the C-terminus of the PNA to improve its water solubility. A short irradiation (visible light) of PNA conjugates with a synthetic DNA resulted in highly efficient photomodulation of the DNA as evidenced by polyacrylamide gel electrophoresis (PAGE). In addition, a PNA-RB conjugate replacing K-PEG8-K with four l-glutamic acids (E4) was found to be photoinactive. Irradiation of active PNA-RB conjugates with synthetic DNA in D20 augments the photoactivity; supporting the involvement of singlet oxygen. PAGE, HPLC, and MALDI-TOF analyses indicate that PNA-DNA photo-cross-linking is a significant pathway in the observed photoreactivity. Selective photo-cross-linking of such PNA-RB conjugates may be a novel approach to selective photodynamic therapy (sPDT) as such molecules would be sequence-specific, cell-permeable, and photoactivated in the visible region.
The Institute for Drug Research, The School of Pharmacy, The Hebrew University of Jerusalem , Hadassah Ein-Kerem, Jerusalem 91120, Israel.
Yossi
Y
Shemesh
The Institute for Drug Research, The School of Pharmacy, The Hebrew University of Jerusalem , Hadassah Ein-Kerem, Jerusalem 91120, Israel.
Eylon
E
Yavin
D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000737:chemistry* / Q000235:genetics; D020135:Peptide Nucleic Acids / Q000737:chemistry* / Q000235:genetics; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000737:chemistry*; D012395:Rose Bengal / Q000737:chemistry*
D004277:DNA, Single-Stranded; D020135:Peptide Nucleic Acids; D017319:Photosensitizing Agents; D012395:Rose Bengal