TMPyP binding evokes a complex, tunable nanomechanical response in DNA.

Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE

Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.

DNA*/chemistry ; DNA*/metabolism ; Optical Tweezers* ; Porphyrins*/chemistry; Bacteriophage lambda/genetics ; DNA, Single-Stranded/metabolism ; DNA, Single-Stranded/chemistry ; DNA, Viral/metabolism ; DNA, Viral/chemistry ; Kinetics ; Nanotechnology/methods ; Sodium Chloride/chemistry ; Sodium Chloride/pharmacology

TMPyP is a porphyrin capable of DNA binding and used in photodynamic therapy and G-quadruplex stabilization. Despite its broad applications, TMPyP's effect on DNA nanomechanics is unknown. Here we investigated, by manipulating λ-phage DNA with optical tweezers combined with microfluidics in equilibrium and perturbation kinetic experiments, how TMPyP influences DNA nanomechanics across wide ranges of TMPyP concentration (5-5120 nM), mechanical force (0-100 pN), NaCl concentration (0.01-1 M) and pulling rate (0.2-20 μm/s). Complex responses were recorded, for the analysis of which we introduced a simple mathematical model. TMPyP binding, which is a highly dynamic process, leads to dsDNA lengthening and softening. dsDNA stability increased at low (<10 nM) TMPyP concentrations, then decreased progressively upon increasing TMPyP concentration. Overstretch cooperativity decreased, due most likely to mechanical roadblocks of ssDNA-bound TMPyP. TMPyP binding increased ssDNA's contour length. The addition of NaCl at high (1 M) concentration competed with the TMPyP-evoked nanomechanical changes. Because the largest amplitude of the changes is induced by the pharmacologically relevant TMPyP concentration range, this porphyrin derivative may be used to tune DNA's structure and properties, hence control the wide array of biomolecular DNA-dependent processes including replication, transcription, condensation and repair.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

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National Excellence Program of the Ministry for Innovation and Technology; Semmelweis University; K135360 Hungarian National Research, Development and Innovation Office; 2020-1.1.6-JÖVŐ-2021-00013 National Heart Program; 2020-4.1.1.-TKP2020 Ministry for Innovation and Technology of Hungary; RRF-2.3.1-21-2022-00003 European Union

9007-49-2 (DNA)
0 (DNA, Single-Stranded)
0 (DNA, Viral)
0 (Porphyrins)
451W47IQ8X (Sodium Chloride)
38673-65-3 (tetra(4-N-methylpyridyl)porphine)

Date Created: 20240629 Date Completed: 20240811 Latest Revision: 20250623

20250623

PMC11317170

10.1093/nar/gkae560

38943349