Project Details
Projekt
De Novo Psoralens for Photo-Additions to DNA & RNA
Subject Area
Physical Chemistry of Molecules, Liquids and Interfaces, Biophysical Chemistry
Organic Molecular Chemistry - Synthesis and Characterisation
Organic Molecular Chemistry - Synthesis and Characterisation
Term
since 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 318058865
Psoralens are herbal compounds with broad therapeutic and diagnostic applications. They may insert themselves between base pairs of ribonucleic acids (DNA and RNA) in a process termed intercalation. Upon photo-excitation intercalated psoralens bind to the bases thymine or uracil. The photo-lesions formed thereby may induce apoptosis of cells. This is the foundation of PUVA (psoralen + UVA-radiation) therapy which treats certain skin diseases and cancers. Under the acronym PARIS (psoralen analysis of RNA interactions and structures), the photo-addition is also utilized for structural studies of RNA. Therapeutic and diagnostic applications would profit from psoralens with higher intercalation affinities and photo-reactivities. Peter Gilch’s group pioneered the investigation of the PUVA process by time-resolved spectroscopy. The effort – in part supported by DFG – revealed the mechanism of the photo-addition. The results provided guidance for the design of improved psoralens. Thomas Müller’s group synthesized a first generation of psoralen derivatives. These exhibited higher intercalation affinities but not yet higher photo-reactivities. Based on these spectroscopic and synthetic experiences, we intend to further improve the psoralen scaffold with respect to PUVA applications. We also will move to structures further apart from this motif like tilted psoralens (angelicins) and furo-derivatives of acridones. Our focus will be the photo-reactivity towards DANN. Depending on the progress also reactions with RNA will be considered. The project will profit from a very close collaboration between spectroscopy and synthesis. It will also receive support from theory (quantum chemistry and molecular dynamics).
DFG Programme
Research Grants
