Development of photoswitchable ligands for the reversible and selective assembly with RNA

Projektinformationen

PHOTORNA

ID Finanzhilfevereinbarung: 749788

DOI 10.3030/749788

Abgeschlossenes Projekt

EK-Unterschriftsdatum 8 März 2017

Startdatum 1 Oktober 2017

Enddatum 31 Dezember 2019

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten € 159 460,80

EU-Beitrag € 159 460,80

Koordiniert durch

UNIVERSITAET SIEGEN
Germany

Ziel

The proposed project aims at the development of novel functional ligands whose association with ribonucleic acid (RNA) is reversibly activated by light. As several RNA forms are essential key elements in physiological processes, the control of their function or malfunction by the reversible binding of photoswitchable ligands possesses a great potential as a tool in anticancer, antiviral and antimicrobial therapy. Surprisingly, this innovative approach towards a controlled reversible generation of RNA binders was mainly neglected in this highly topical research field. Hence, in this project photochromic hemi-indigo and fulgide derivatives are chosen as a platform for the design of photo-responsive RNA ligands, because i) they exhibit general features of RNA binders; ii) their structure can be reversibly modified by light, iii) the core structures are readily synthesized, and iii) the substitution pattern can be easily varied to enable fine-tuning of binding selectivity based on structure-activity relationships. In addition, conjugates that comprise two photoactive RNA-binding units will be obtained and studied because such bifunctional binders are expected to have very high affinity and selectivity toward RNA. An extensive library of derivatives will be synthesized and tested for their photocontrollable association with RNA. As a special method, real-time NMR-spectroscopic studies with direct irradiation of the sample inside a specifically designed spectrometer will be used to assess in detail the dynamics in the course of the photoinduced ligand–RNA interactions. Overall, it is anticipated that this systematic approach will enable the identification and development of lead structures for controllable RNA-targeting drugs with a great pharmacological potential. Moreover, the high interdisciplinary, innovative character of this challenging project gives the researcher an excellent opportunity to achieve professional maturity and open up best career possibilities.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › biochemistry › biomolecules › nucleic acids
• natural sciences › chemical sciences › physical chemistry › photochemistry
• medical and health sciences › health sciences › infectious diseases › RNA viruses › HIV
• medical and health sciences › clinical medicine › oncology
• natural sciences › biological sciences › genetics › RNA

Programm/Programme

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Thema/Themen

• MSCA-IF-2016 - Individual Fellowships

Aufforderung zur Vorschlagseinreichung

H2020-MSCA-IF-2016

Finanzierungsplan

MSCA-IF-EF-ST - Standard EF

Koordinator

UNIVERSITAET SIEGEN

• Netto-EU-Beitrag: € 159 460,80
• Adresse: ADOLF REICHWEIN STRASSE 2A ; 57076 Siegen ; Deutschland
• Region: Nordrhein-Westfalen › Arnsberg › Siegen-Wittgenstein
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 159 460,80