1. Academic Validation
  2. Spectroscopic view on the interaction between the psoralen derivative amotosalen and DNA

Spectroscopic view on the interaction between the psoralen derivative amotosalen and DNA

  • Photochem Photobiol Sci. 2024 Mar 8. doi: 10.1007/s43630-024-00545-2.
Michelle P Rademacher 1 Tim Rohn 1 Wiebke Haselbach 1 A Theresa Ott 1 Peter W Bringmann 2 Peter Gilch 3
Affiliations

Affiliations

  • 1 Institut für Physikalische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany.
  • 2 Cerus Corporation, 1220 Concord Avenue, Concord, CA, 94520, USA.
  • 3 Institut für Physikalische Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany. gilch@hhu.de.
Abstract

Psoralens are eponymous for PUVA (psoralen plus UV-A radiation) therapy, which inter alia can be used to treat various skin diseases. Based on the same underlying mechanism of action, the synthetic psoralen amotosalen (AMO) is utilized in the pathogen reduction technology of the INTERCEPT® Blood System to inactivate pathogens in plasma and platelet components. The photophysical behavior of AMO in the absence of DNA is remarkably similar to that of the recently studied psoralen 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT). By means of steady-state and time-resolved spectroscopy, intercalation and photochemistry of AMO and synthetic DNA were studied. AMO intercalates with a higher affinity into A,T-only DNA (KD = 8.9 × 10-5 M) than into G,C-only DNA (KD = 6.9 × 10-4 M). AMO covalently photobinds to A,T-only DNA with a reaction quantum yield of ΦR = 0.11. Like AMT, it does not photoreact following intercalation into G,C-only DNA. Femto- and nanosecond transient absorption spectroscopy reveals the characteristic pattern of photobinding to A,T-only DNA. For AMO and G,C-only DNA, signatures of a photoinduced electron transfer are recorded.

Keywords

Amotosalen; DNA intercalation; Pathogen reduction technology; Photoaddition; Photoinduced electron transfer; Time-resolved spectroscopy.

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