Guanosine-borate hydrogels- Form and function

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Peters, Gretchen Marie
Davis, Jeffery T
Due to their biocompatibility and stimuli-responsive nature, supramolecular hydrogels derived from natural products are attractive for a number of biomedical applications, including diagnostics, targeted drug delivery and tissue engineering. Nucleosides, the building blocks of nucleic acids, are desirable candidates for forming supramolecular gels as they readily engage in reversible, noncovalent interactions. Guanosine (G 1), in particular, is unique in that it has multiple faces for noncovalent interactions and can self-associate into stable higher-order assemblies, such as G4-quartets and G-quadruplexes. This self-assembly of G 1 and its derivatives into G4-quartets has long been known to induce hydrogelation. However, the requirement of excess salt and the propensity of G 1 to crystallize persist as limitations for G4-hydrogels. Thus, recent interest has focused on developing G4-hydrogels with improved lifetime stabilities and lower salt concentrations. The work described here focuses on a long-lived G4-hydrogel made from G 1 and 0.5 equiv. of KB(OH)4. Gelation occurs through the formation of guanosine-borate (GB) diesters and subsequent assembly into cation-templated G4•K+-quartets. The physical properties and stability of the GB hydrogel can be readily manipulated by varying the gelation components. For example, merely altering the identity of the cation drastically alters the gel’s physical properties. Namely, while GB hydrogels formed with K+ are self-supporting and robust, mixing G 1 with LiB(OH)4 results in a weak gel that readily dissociates upon physical agitation. Small molecules, such as cationic dyes and nucleosides, could be selectively incorporated into the GB hydrogel through reversible noncovalent and covalent interactions. One such dye and known G4-quartet binding ligand, thioflavin T (ThT) fluoresces in the presence of the GB hydrogel. The ThT fluorescence increases as a function of gelator concentration with a sharp increase correlating to the gel point. Thus, this ThT fluorescence assay is a new method for probing the formation of G4-hydrogels. Additionally, ThT acts as a molecular chaperone for Li+ GB hydrogelation. Substoichiometric amounts of ThT results in faster hydrogelation, increased gel strength and improved recovery of a hydrogel destroyed by external stress. Insights gained from this research have implications towards development of biomaterials, biomolecule sensing, and drug delivery.