User talk:Rhijazi00/sandbox

Formation

Intercalated motif (i-motif) DNA is formed in the nuclei of cells via a stack of intercalating hemi-protonated C-neutral C base pairs, which are optimized at a slightly negative pH. In vitro, i-motifs have been characterized with indications that the DNA is derived from telomeres. Using a variety of biophysical techniques, i-motif DNA has been characterized to be derived from centromeres and promoter regions of proto-oncogenes. An analysis of the biophysical results shows the overall stability of the structures is dependent on the number of cytosines in the i-motif core and length and composition of loops in the formation of both intramolecular and intermolecular structures.

          	Although it has been largely established that C-rich sequences can form i-motif structures in vitro, there is still significant debate regarding the in vivo existence of four-stranded i-motif DNA structure in the human genome.  It has been confirmed that-motif DNA in vivo can be formed at physiological pH under certain conditions of molecular crowding and negative superhelicity induced during transcription. Recent studies have shown that the formation of i-motif DNA by specific genomic sequences can occur at neutral pH. Numerous studies have demonstrated that i-motif DNA has an effect on replication and transcription in DNA processing. 

Ligands and Binding Sites

Ligands/ Binding sites:

Tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4)

The first study determined a ligand binding to i-motif DNA was by Hurley and colleagues in 2000 when they researched the interaction between Tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4) and tetramolecular i-motif DNA isolated from a human telomeric sequence. Hurley and colleagues utilized an electrophoretic mobility shift assay (EMSA) by notably not changing the DNA melting temperature. This ligand interacts with G4 on the i-motif sequence to deregulate c-myc expression and inhibit telomerase. Two molecules TMPyP4 coordinates with i-motif DNA on both the top and bottom of its structure as determined by NMR experiments.

Phenanthroline and Acridine Derivatives

Macrocyclic Tetraoxazoles, L2H2-4OTD

Mitoxantrone, Tilorone and Tobramycin

Carboxylic Acid-Modified Single-Walled Carbon Nanotubes (SWCNTs) and Graphene Quantum Dots (GQDs)

Ligands used for Biological Function There are several ligands for i-motif that are used for biological function. These include IMC-48, IMC-76, Nitidine, NSC309874, acridone derivative, and PBP1. IMC-48 stabilizes the bcl-2 structure of i-motif by upregulating bcl-2 gene expression. IMC-76 stabilizes the bcl-2 hairpin structure by downregulating the bcl-2 gene expression. Nitidine destabilizes the hairpin on hybride i-motif/hairpin structure and has no significant interactions with complementary G4. Nitidine downregulates the k-ras gene expression by showing selectivity toward the k-ras structure. NSC309874 stabilizes the PDGFR-b i-motif structure with no significant interaction with complementary G4 in order to downregulate the PDGFR-b gene expression. Acridone derivative stabilizes the c-myc i-motif structure with no significant interaction with G4 in order to downregulate the c-myc gene expression. PBP1 stabilizes the bcl-2 i-motif structure and promotes its formation in neutral pHs to upregulate the bcl-2 gene expression.

Ligands used as Fluorescent Probes

The ligands for i-motif that are used as fluorescent probes include Thiazole orange, 2,2′-diethyl-9-methylselenacarbocyanine bromide (DMSB), crystal violet, berberine. neutral red, thioflavin T, and perylene tetracarboxylic acid diimide derivative (PTCDI). 

Rhijazi00 (talk) 04:36, 10 December 2020 (UTC)

1. Wright, E. P., Huppert, J. L., & Waller, Z. (2017). Identification of multiple genomic DNA sequences which form i-motif structures at neutral pH. Nucleic acids research, 45(6), 2951–2959. https://doi.org/10.1093/nar/gkx090 2.Sushmita Nautiyal; Vishal Rai; Sudipta Bhat; Ravi Kumar; Mudasir Mohd Rather; M.Sankar. I-Motif Dna: Significance and Future Prospective. Exploratory Animal and Medical Research 2020, 10 (1), 18–23. 3. Yang B, Rodgers MT (2014) Base-pairing energies of protonbound heterodimers of cytosine and modified cytosines: implications for the stability of DNA i-motif conformations. J Am Chem Soc 136(1): 282-90. 4.Masoud, Shadi Sedghi, and Kazuo Nagasawa. "I-motif-binding ligands and their effects on the structure and biological functions of i-motif." Chemical and Pharmaceutical Bulletin 66.12 (2018): 1091-1103.