PhD Scientific Days 2022

Molecular Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Porphyrin binding by DNA as a function of ionic strength and chain mechanics

Előadó neve

Kretzer, Balázs

Előadó munkahelye

Department of Biophysics and Radiation Biology, Semmelweis University

Előadó telefonszáma

30/500-79-71

Előadó e-mail címe

kretzer.b1@gmail.com

Az előadás címe

Porphyrin binding by DNA as a function of ionic strength and chain mechanics

Szerző(k) neve és munkahelye

Balázs Kretzer1, Levente Herényi1, Gabriella Csík, Bálint Kiss1 and Miklós Kellermayer1
1 Department of Biophysics and Radiation Biology, Budapest

Bemutatás módja

Poszter

Szekció

Molecular Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Molecular Sciences

Összefoglaló szövege

Porphyrins and their derivatives have been the subject of numerous studies due to their role in photodynamic therapy. Cationic derivatives – such as tetrakis(4-N-methyl)pyridyl-porphyrin (TMPYP) which is the subject of the current research — have, in addition, a broad spectrum of antimicrobial activity. TMPYP has strong affinity for DNA, and it is also the subject of investigations for its properties to interact with G-quadruplexes, which may increase its role in cancer treatment. TMPYP can bind to DNA in different ways: it can intercalate between base pairs or bind into the grooves. Whichever mechanism dominates is affected by the relative binding constants. Furthermore, it is highly likely that the mechanical status of DNA has a significant influence on TMPYP binding. To investigate the latter, we explored TMPYP-DNA binding at the single molecule level while adjusting the conditions that may have an impact on the binding process (e.g., ionic strength, DNA stretch rate). Thus, conclusions may be drawn regarding both the structural changes of DNA and the dynamics of TMPYP binding.
Measurements on λ-phage DNA were carried out by using an optical tweezers instrument combined with a microfluidic device. DNA was first stretched in buffer at constant speed, then the molecule was moved into the microfluidic channel containing TMPYP where it was stretched again with the same speed. Measurements were performed at 3 different NaCl concentrations and 3 DNA stretching speeds at several TMPYP concentrations. More than 500 different DNA molecules were measured in the experiment. Force-distance curves showed major structural changes in DNA due to TMPYP binding. Varying the measurement conditions have also caused different alterations in DNA structure and in the dynamics of the binding. We developed a model to mathematically describe the force-distance curve of the DNA, with which we were able categorize the effects TMPYP had on λ-DNA within the experimental parameter space. The results of our research on DNA-TMPYP interaction provide a good ground for understanding the binding process and the impact it has on the structure of DNA. Furthermore, it can serve as a basis for the development of additional conjugates for medical therapies.
Funding: (ÚNKP-21-3-II-SE-37); TKP2021-EGA-23; National Research, Development and Innovation Office, Ministry for Innovation and Technology.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Prof. Dr. Miklós Kellermayer

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4176

Start

13:05

End

13:10

Authors (legacy)

Balázs Kretzer1, Levente Herényi1, Gabriella Csík, Bálint Kiss1 and Miklós Kellermayer1
1 Department of Biophysics and Radiation Biology, Budapest