Interaction of Human Telomeric i-Motif DNA with Single-Walled Carbon Nanotubes: Insights from Molecular Dynamics Simulations

Abstract

This work deals with molecular dynamics simulations of human telomeric i-motif DNA interacting with functionalized single-walled carbon nanotubes. We study two kinds of i-motifs differing by the protonation state of cytosines, i.e., unprotonated ones representative to neutral pH and with half of the cytosines protonated and representative to acidic conditions. These i-motifs interact with two kinds of carbon nanotubes differing mainly in chirality (diameter), i.e., (10, 0) and (20, 0). Additionally, these nanotubes were on-tip functionalized by amino groups or by guanine- containing residues. We found that protonated i-motif adsorbs strongly, although not specifically, on the nanotube surfaces with its 3’ and 5’ ends directed toward the surface and that adsorption does not affect the i-motif shape and hydrogen bonds existing between C:C+ pairs. The functional groups on the nanotube tips have minimal effect either on position of i-motif or on its binding strength. Unprotonated i-motif, in turn, deteriorates significantly during interaction with the nanotubes and its binding strength is rather high as well. We found that (10, 0) nanotubes destroy the i-motif shape faster than (20, 0). Moreover the i-motif either tries to wrap the nanotube or migrates to its tip and becomes immobilized due to interaction with guanine residue localized on the nanotube tip and attempts to incorporate its 3’ end into the nanotube interior. No hydrogen bonds exist within the unprotonated i-motif prior to and after adsorption on the nanotube. Thus, carbon nanotubes do not improve the stability of unprotonated i-motif due to simple adsorption or just physical interactions. We hypothesize that the stabilizing effect of carbon nanotubes reported in the literature is due to proton transfer from the functional group in the nanotube to cytosines and subsequent formation of C:C+ pairs.

Carbon Nanotubes and Short Cytosine-Rich Telomeric DNA Oligomeres as Platforms for Controlled Release of Doxorubicin—A Molecular Dynamics Study

“…That kind of functionalization was described in literature [27] and involves carboxylation and subsequent derivatization with N'9-(2-aminoethyl) guanine. Preparation methodology of the molecular model of the functionalized nanotube was the same as already described in one of our recent publications [28]. Shortly, we first prepared a template of the guanine containing residue with only one aromatic ring cut off the CNT structure.…”

The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

“…i-Motif stabilization by SWNTs causes the uncapping of telomeres and induces a DNA damage response localized to the telomeres that eventually initiates cell cycle arrest, apoptosis, or senescence. Subsequent evidence suggests that the mechanism for SWNT stabilization of i-motifs involves the proton exchange between the carboxyl group on the SWNT and the i-motif cytosines, resulting in hemi-protonation of the i-motif-forming sequences and folding of a stable structure [81]. SWNTs have received attention as potential drug delivery devices and their ability to inhibit telomerase via i-motif stabilization and induce anti-proliferative effects hints at an additional intriguing potential strategy for future cancer therapeutics [80].…”

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

“…Carbon Dots - (Erimban and Daschakraborty, 2020) Carbon Nanotubes - (Panczyk et al, 2013(Panczyk et al, , 2020Izadyar et al, 2016;Li et al, 2016a;Rungrotmongkol and Poo-arporn, 2016;Hashemzadeh and Raissi, 2017;Kamel et al, 2017;Wolski et al, 2017aWolski et al, , 2018Wolski et al, , 2020Wolski et al, , 2019Zaboli and Raissi, 2017;Karnati and Wang, 2018;Kavyani et al, 2018a,b;Zhang et al, 2018;Contreras et al, 2019;Dehneshin et al, 2019;Mortazavifar et al, 2019;Kordzadeh et al, 2019;Ghadri et al, 2020;Maleki et al, 2020;Pakdel et al, 2020;Pennetta et al, 2020) Dendrimers - (Kojima et al, 2000;Lee et al, 2002Maiti and Bagchi, 2006;Lee and Larson, 2008Vasumathi and Maiti, 2010;Nandy and Maiti, 2011;Huynh et al, 2012;Nandy et al, 2012Nandy et al, , 2013Jain et al, 2013Jain et al, , 2016Kłos and Sommer, 2013;Tian and Ma, 2013;Tu et al, 2013;Martinho et al, 2014;Wen et al, 2014;Jiang et al, 2015;…”

“…(1) behavior of the nanoparticle in the bloodstream and the protective polymer corona, (2) drug loading and release and (3) nanoparticle interaction with lipid membranes and entry into the cell. We would like to here alert the reader to the fact that there are other reviews of aspects of the use of computational Drugs, theirs applications, and references 5-flouracil -anti-cancer drug (Barraza et al, 2015;Kacar, 2019) Albendazole -anti-worm drug (Rodríguez-Hidalgo et al, 2011) Amphotercin B -antifungal drugs (Mobasheri et al, 2016) Anakinra -used in arthritis therapy (Liebner et al, 2014) Camptothecin -chemotherapy agent (Ansari et al, 2018;Alinejad et al, 2020) Carmustine -chemotherapy agent (Wolski et al, 2017a;Mortazavifar et al, 2019) Chlortetracycline -antibiotic (Dowlatabadi et al, 2019) Cisplatin -chemotherapy agent (Panczyk et al, 2013) Curcurbitacin drug families (Patel et al, 2010a) Cyclosporine -immunosuppressant (Tokarský et al, 2011) Dicolofenac -anti-inflammatory agents (Karjiban et al, 2012) Doxorubicin -chemotherapy agent (Guo et al, 2010(Guo et al, , 2012bYang et al, 2012;Yang C. et al, 2019;Yang Y.-L. et al, 2019;Zhang et al, 2012Zhang et al, , 2014Zhang et al, , 2018Nie et al, 2013;Shan et al, 2014;Izadyar et al, 2016;Rungrotmongkol and Poo-arporn, 2016;Wolski et al, 2017bWolski et al, , 2018Wolski et al, , 2019Hu et al, 2017;Mousavi et al, 2018;Kordzadeh et al, 2019;Alinejad et al, 2020;Exner and Ivanova, 2020;…”