Preprint Brief Report Version 1 Preserved in Portico This version is not peer-reviewed

The Spectrofluorometric Determination of DNA Binding Constants for Several Psoralen Derivatives

Version 1 : Received: 29 December 2023 / Approved: 3 January 2024 / Online: 3 January 2024 (05:40:18 CET)

How to cite: Balas, A.; Gasparro, F.P. The Spectrofluorometric Determination of DNA Binding Constants for Several Psoralen Derivatives. Preprints 2024, 2024010128. https://doi.org/10.20944/preprints202401.0128.v1 Balas, A.; Gasparro, F.P. The Spectrofluorometric Determination of DNA Binding Constants for Several Psoralen Derivatives. Preprints 2024, 2024010128. https://doi.org/10.20944/preprints202401.0128.v1

Abstract

Psoralens have been used in the treatment of several skin diseases such as psoriasis and atopic eczema through PUVA (psoralen + UVA), cutaneous T-cell lymphoma through ECP (extracorporeal photochemotherapy), and recently, the treatment of solid tumors through X-PACT (x-ray psoralen activated cancer therapy). Ingesting psoralens and exposing the molecules to UVA light allows for the flat-planar psoralens to intercalate or slide in-between base pairs and then to form photo-adducts with the DNA backbone which can stop or slow DNA replication. The intrinsic ability of psoralens to bind with DNA and their therapeutic effectiveness contribute to the increased interest in the study of these molecules. Several studies measuring psoralen-DNA binding capabilities have used a variety of spectroscopic techniques and different experimental conditions. In this study, spectrofluorometry was used to measure the DNA-binding capabilities of three different psoralen derivatives (6E, AMT and 8-MOP) under identical experimental conditions. The binding constants were 0.325x106 M-1 for 8-MOP, 0.516x106 M-1 for AMT, and 7.30x106 M-1 for 6E. This direct comparison of the three different psoralens demonstrated the impact of their molecular structure on the DNA-binding capacity. 6E’s significantly greater binding constant makes it the stronger candidate for further studies looking into potential applications for cancer treatment.

Keywords

Psoralen; Calf-thymus; Oligo (dAdT); Fluorometry; 8-Methoxypsoralen (8-MOP); Aminomethlytrimethylpsoralen (AMT); 6E; Photochemotherapy; Binding; Scatchard; DNA (AT-40)

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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