José’s comment on: Intelligent, Biodegradable, and Self-Healing Hydrogels Utilizing DNA Quadruplexes

By José M. Martinez

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This paper is about making of a water based gel made from the supramolecular interactions of guanosine rich oligonucleotides. They attached these oligonucleotides symmetrically into the ends of PEG chains of variable lengths and conformations. This was made through High Efficiency Liquid Phase (HELP) synthesis. This synthetic strategy, as its name says, occurs in a liquid phase instead of the usual solid phase synthesis. The purpose of this is to allow them to obtain greater quantities of product more easily without risking the effectiveness. These DNA-PEG-DNA monomers have the ability, when diluted and presented with a cation (K+ or Na+), to self-assemble its DNA moieties through non-covalent interactions to for G-quadruplexes. Those strong interactions change the physical properties of the solution by forming a hydrogel. In the study, it was proven that the concentration of the cation required to trigger the self-assembly is relatively small. It is even compared to the concentration of salts found in body-related fluids like sweat, saliva, and tears. The hydrogel also has the capability to heal itself and interact by diffusion with another of the same kind. Finally, it was found that by adding a few extra nucleotides to the DNA moiety of the monomer and a matching strand for that part, the G-quadruplexes could be disassembled, returning the gel back to its liquid phase. All the previously stated properties indicate potential uses of this hydrogel for biomedical purposes.
Regarding myself, I learned mostly about the molecular aspect of gels and how they are formed. It was very interesting seeing the role that the supramolecular interactions played in the formation of this particular gel and the experiments made to investigate further into its properties.

JMM: Tanaka, 2017. Intelligent, Biodegradable, and Self-Healing Hydrogels Utilizing DNA Quadruplexes

Our last three papers…

mAGi16-Top2_whiteBelow are the references to our last three papers. I will post a brief overview of each one soon, but in the meantime:

Structural studies of supramolecular G-quadruplexes formed from 8-aryl-2’-deoxyguanosine derivatives. García-Arriaga, M.; Hobley, G.; Rivera, J. M.,  J. Org. Chem.2016, 81, Advance Online Publication; DOI: 10.1021/acs.joc.6b01113. PMID: 27303787

  • The first 50 people can download a free reprint of the paper directly from the publisher by going to this link.
  • Abstract. Self-assembly is a powerful tool for the construction of complex nanostructures. Despite the advances in the field, the development of precise self-assembled structures remains a challenge. We have shown that in the presence of suitably sized cations like K+, 8-aryl-2′-deoxyguanosine (8ArG) derivatives self-assemble into sets of coaxially stacked planar tetramers, we term supramolecular G-quadruplexes (SGQs). Previously, we reported that when the 8-aryl group is a phenyl ring with a meta-carbonyl group, the resulting supramolecule is a hexadecamer, which is remarkably robust as illustrated by its isostructural assembly in both organic and aqueous environments. We report here a detailed three-dimensional structure of the SGQs formed by lipophilic, and hydrophilic, 8ArG derivatives with either 8-(meta-acetylphenyl), 8-(para-acetylphenyl), and 8-(meta-ethoxycarbonylphenyl) groups. The chirality and close contacts between the subunits impose different levels of steric and electrostatic constraints on opposite sides of the tetrads, which determine their preferred relative orientation. The balance between attractive non-covalent interactions juxtaposed with repulsive steric and electrostatic interactions explains the high cooperativity, fidelity and stability of these SGQs. These structural studies, together with titration experiments and molecular dynamics simulations provide insight on the mechanism of formation of these SGQs.

Organic Nanoflowers From a Wide Variety of Molecules Templated By A Hierarchical Supramolecular Scaffold. Negrón, L. M.; Diaz, T. L.; Ortiz-Quiles, E. O.; Dieppa, D.; Madera-Soto, B.; Rivera, J. M., Langmuir 2016, 32 (10), 2283–2290. DOI: 10.1021/acs.langmuir.5b03946; PMCID: PMC4896646

  • Abstract. Nanoflowers (NFs) are flowered-shaped particles with overall sizes or features in the nanoscale. Beyond their pleasing aesthetics, NFs have found a number of applications ranging from catalysis, to sensing, to drug delivery. Compared to inorganic based NFs, their organic and hybrid counterparts are relatively underdeveloped mostly because of the lack of a reliable and versatile method for their construction. We report here a method for constructing NFs from a wide variety of biologically relevant molecules (guests), ranging from small molecules, like doxorubicin, to biomacromolecules, like various proteins and plasmid DNA. The method relies on the encapsulation of the guests within a hierarchically structured particle made from supramolecular G-quadruplexes. The size and overall flexibility of the guests dictate the broad morphological features of the resulting NFs, specifically, small and rigid guests favor the formation of NFs with spiky petals, while large and/or flexible guests promote NFs with wide petals. The results from experiments using confocal fluorescence microscopy, and scanning electron microscopy provides the basis for the proposed mechanism for the NF formation.

Tuning Thermoresponsive Supramolecular G-Quadruplexes. José E. Betancourt & José M. Rivera, Langmuir 2015, 31 (7), 2095-2103. DOI:10.1021/la504446k; PMCID: PMC4863471 [Free PMC Article]

  • Abstract. Thermoresponsive systems are attractive due to their suitability for fundamental studies as well as their practical uses in a wide variety of applications. While much progress has been achieved using polymers, alternative strategies such as the use of well-defined nonpolymeric supramolecules are still underdeveloped. Here we report three 8-aryl-2′-deoxyguanosine derivatives (8ArGs) that self-assemble in aqueous media into precise thermoresponsive supramolecular G-quadruplexes (SGQs). We report the synthesis of such derivatives, studies of their isothermal self-assembly, and the thermally induced assembly to form higher-order meso-globular assemblies we term supramolecular hacky sacks (SHS). The lower critical solution temperature (LCST) that indicates the formation of the SHS was modulated by changing (a) intrinsic parameters (i.e., structure of the 8ArGs); (b) extrinsic parameters such as the salt used to promote the formation of the SGQ; and (c) supramolecular parameters such as the coassembly different 8ArGs to form heteromeric SGQs. Changes in the intrinsic parameters lead to LCST variations in the range of 28–59 °C. Modulating extrinsic parameters such as replacing KI with KSCN abolishes the thermoresponsive phenomenon whereas changing the cation from K+ to Na+or adjusting the pH (in the range of 6–8) has negligible effects on the LCST. Modulating supramolecular parameters results in transition temperatures that are intermediate between those obtained by the respective homomeric SGQs, although the specific proportions of the subunits are critical in determining the reversibility of the process. Given the extensive applications of thermoresponsive polymers, the nonpolymeric supramolecular counterparts presented here may represent an attractive alternative for fundamental studies and biorelevant applications.