FapydG in the Shadow of OXOdG—A Theoretical Study of Clustered DNA Lesions

Karwowski, Bolesław T.

doi:10.3390/ijms24065361

Cited by 6 publications

(5 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the above and as OXO G 4 C 2 has the lowest ionization potential, this base pair can be assigned as the radical cation sink during electron hole transfer. This is in good agreement with previous observations [ 43 , 69 , 70 ]. No differences between oligo-RcdG and oligo-ScdG in the discussed values were observed.…”

Section: Resultssupporting

confidence: 94%

The Influence of 5′,8-Cyclo-2′-Deoxyguanosine on ds-DNA Charge Transfer Depends on Its Diastereomeric Form: A Theoretical Study

Karwowski

2023

Antioxidants

Self Cite

View full text Add to dashboard Cite

The genetic information stored in the nucleobase sequence is continuously exposed to harmful extra- and intra-cellular factors, which can lead to different types of DNA damage, with more than 70 lesion types identified so far. In this article, the influence of a multi-damage site containing (5′R/S) 5′,8-cyclo-2′-deoxyguanosine (cdG) and 7,8-dihydro-8-oxo-2′-deoxyguanosine (OXOdG) on charge transfer through ds-DNA was taken into consideration. The spatial geometries of oligo-RcdG: d[A1(5′R)cG2A3OXOG4A5]*d[T5C4T3C2T1] and oligo-ScdG: d[A1(5′S)cG2A3OXOG4A5]*d[T5C4T3C2T1] were optimized at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the aqueous phase using ONIOM methodology. For all the electronic property energies under discussion, the M06-2X/6-31++G** level of theory was used. Additionally, the non-equilibrated and equilibrated solvent-solute interactions were into consideration. The obtained results confirm the predisposition of OXOdG to radical cation formation regardless of the presence of other lesions in a ds-DNA structure. In the case of electron transfer, however, the situation is different. An excess electron migration towards (5′S)cdG was found to be preferred in the case of oligo-ScdG, while in the case of oligo-RcdG, OXOdG was favored. The above observation was confirmed by the charge transfer rate constant, vertical/adiabatic ionization potential, and electron affinity energy values, as well as the charge and spin distribution analysis. The obtained results indicate that 5′,8-cyclo-2′-deoxyguanosine, depending on the C5′ atom chirality, can significantly influence the charge migration process through the double helix. The above can be manifested by the slowdown of DNA lesion recognition and removal processes, which can increase the probability of mutagenesis and subsequent pathological processes. With regard to anticancer therapy (radio/chemo), the presence of (5′S)cdG in the structure of formed clustered DNA damage can lead to improvements in cancer treatment.

show abstract

Section: Resultssupporting

confidence: 94%

The Influence of 5′,8-Cyclo-2′-Deoxyguanosine on ds-DNA Charge Transfer Depends on Its Diastereomeric Form: A Theoretical Study

Karwowski

2023

Antioxidants

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the genome, during the oxidizing process, dG can be converted from OXO dG to OX Ia via several “intermediate” products, as shown in Figure 1 . These two lesions are formed in the cell in normoxia conditions, while in hypoxia, the Fapy dG formation is preferred [ 49 ]. Because of the differences in the structure and electronic properties, OXO dG and OX Ia probably demonstrate a different influence on charge transfer through ds-oligo.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Oxidized Imino-Allantoin in the Presence of OXOG on Double Helix Charge Transfer: A Theoretical Approach

Karwowski

2024

IJMS

Self Cite

View full text Add to dashboard Cite

The genome is continuously exposed to a variety of harmful factors that result in a significant amount of DNA damage. This article examines the influence of a multi-damage site containing oxidized imino-allantoin (OXIa) and 7,8-dihydro-8-oxo-2′-deoxyguanosine (OXOdG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[A1OXIa2A3OXOG4A5]*d[T5C4T3C2T1] structure was obtained at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the condensed phase, with the energies obtained at the M06-2X/6-31++G** level. The non-equilibrated and equilibrated solvent-solute interactions were also considered. Theoretical studies reveal that the radical cation prefers to settle on the OXOG moiety, irrespective of the presence of OXIa in a ds-oligo. The lowest vertical and adiabatic ionization potential values were found for the OXOG:::C base pair (5.94 and 5.52 [eV], respectively). Conversely, the highest vertical and adiabatic electron affinity was assigned for OXIaC as follows: 3.15 and 3.49 [eV]. The charge transfers were analyzed according to Marcus’ theory. The highest value of charge transfer rate constant for hole and excess electron migration was found for the process towards the OXOGC moiety. Surprisingly, the values obtained for the driving force and activation energy of electro-transfer towards OXIa2C4 located this process in the Marcus inverted region, which is thermodynamically unfavorable. Therefore, the presence of OXIa can slow down the recognition and removal processes of other DNA lesions. However, with regard to anticancer therapy (radio/chemo), the presence of OXIa in the structure of clustered DNA damage can result in improved cancer treatment outcomes.

show abstract

“…When the hydroxyl free radical (•OH) interacts at the level of the puric bases, a modification occurs at the C8 position of the guanine ring, generating a radical that can be oxidized to 8-hydroxy-2 -deoxyguanosine (8-OHdG) or reduced to 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy G) [106]. These resulting products are highly mutagenic and capable of inducing a G:C to T:A transversion, with 8-OHdG being recognized as an important marker of oxidative DNA damage due to its easy detection [107].…”

Section: Oxidative Stress and Antioxidant Defense System (Ads)mentioning

confidence: 99%

Effect of Regular Consumption of a Miraculin-Based Food Supplement on Taste Perception and Nutritional Status in Malnourished Cancer Patients: A Triple-Blind, Randomized, Placebo-Controlled Clinical Trial-CLINMIR Pilot Protocol

López-Plaza,

Gil,

Menéndez-Rey

et al. 2023

Nutrients

View full text Add to dashboard Cite

Taste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB, or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, the fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols. The clinical trial protocol has been registered at the platform for Clinical Trials (NCT05486260).

show abstract

FapydG in the Shadow of OXOdG—A Theoretical Study of Clustered DNA Lesions

Cited by 6 publications

References 58 publications

The Influence of 5′,8-Cyclo-2′-Deoxyguanosine on ds-DNA Charge Transfer Depends on Its Diastereomeric Form: A Theoretical Study

The Influence of 5′,8-Cyclo-2′-Deoxyguanosine on ds-DNA Charge Transfer Depends on Its Diastereomeric Form: A Theoretical Study

The Influence of Oxidized Imino-Allantoin in the Presence of OXOG on Double Helix Charge Transfer: A Theoretical Approach

Effect of Regular Consumption of a Miraculin-Based Food Supplement on Taste Perception and Nutritional Status in Malnourished Cancer Patients: A Triple-Blind, Randomized, Placebo-Controlled Clinical Trial-CLINMIR Pilot Protocol

Contact Info

Product

Resources

About