Functionalized Glycomolecules Based On "Click Chemistry":Constructions And Applications

"Click Chemistry" is characteristic of the formation of stable "C-X-C" bonding center. Ranging from unimolecule construction to combinational chemistry, from structural multiformity to functional diversification, click chemistry opens up a series of novel synthetic methods, which is widely applicable and highly creative, with the advantages of convenient implementation, modularization, fast reactivity, high yields, excellent stereoselectivity and insensitivity to water and oxygen. Prominent category as it is, copper(I) catalyzed Huisgen azide-alkyne1,3-dipolar cycloaddition (CuAAC) reaction shows great superiority in the synthesis of functionalized glycomolecules. In this dissertation,"1,2,3-riazole" linked glycomolecules with structural diversity and multifunction were fabricated on the basis of click chemistry, and the research content can be divided into3sections as follows:Section One(Chapter2of the dissertation):Glycolipids in nature include all amphiphilic compounds with diversified structures and complicated functions, which mainly consist of hydrophilic sugars and hydrophobic lipids connecting with each other in different ways. Besides the constructive roles in life, they functions as informational and regulating molecules, participating in various biological processes. Moreover, numerous natural and synthetic sugar-lipid derivatives possess comprehensive bioactivities such as anticancer, antibiosis and immunoregulating, and their remarkable surface chemical properties endow them with important applications in industry.In our research, simple glycosyl and lipidic ligands were "clicked" together via CuAAC method to construct series of1,2,3-triazole linked glycolipids with regular changes in their structures. In the subsequent anticancer activity assessments,"structure-activity relationships" were partly displayed by compound series Ⅰ and Ⅱ, and "synergetic effect" was found in series Ⅱ. Besides, antibacteria results were acquired from series Ⅰ. In the physicochemical study, some interesting interfacial qualities were found on series Ⅰ and Ⅱ, and improved anticorrosion ability was achieved on series Ⅲ, whose structures were based on reformational modifications of series I and II compounds.Section Two(Chapter3of the dissertation):The specific recognition between multifarious sugars and their corresponding receptor proteins in nature layes the foundation of biological functions of sugars which can be effectively realized via the joint interactions between multicopied glycans and clustered receptors, namely "multivalent effect" or "clustered effect". A large amount of artificial glycoclusters and glycopolymers targeted their receptors successfully by utilizing the effect.In this work, we aimed at constructing novel glycoclusters with multiple glycones. Unnatural "oxygen peptido-skeletons" with multiple azides were firstly concatenated by "peptidoxy" bonds. Glycosyl alkynes of biological importance were synthesized thereafter to "click" onto the skeletons via CuAAC in order to abtain1,2,3-triazolyl "glycosyl aminoxy acid" and "glycosyl oxygen peptides". These sugar derivatives possess modifiable carboxyl and amino groups that are convinent for further functionalization. The equipped GalNAc residues endow them with the biological targeting ability and features of tumor vaccine molecules, which is benefit for biological and medical applications.Section Three(Chapter4of the dissertation):On appearing of the new two dimensional nano material, graphene has been leading the way of sensing nanoscience into a brand-new era. Not only the splendid optical, electrical and structural properties endow it with wide utilizations, but the high biocompatibility and low toxicity also make it advantageous in biological and medical applicabilities. During the short10years since its appearance, innumerable new sensing nanoplatforms based on graphene have been competitively reported, which showed great applicable values in detection and diagnosis.In this research, bio-recognizable sugars were connected with excellently fluorescent rhodamine group using click chemistry to get glycosyl rhodamine fluorophors which were stacked onto graphene oxide through π-π interaction in order to obtain clustered glycosyl fluorophors on the surface and FRET effect driving "light off" biological sensing platforms. Then, we conveniently conducted the "light on" detection of sugar specific lectins by the mechanism that sugar-protein interaction can impede the FRET effect. On the basis of this system, in suit recognition and fluorescent labeling of sugar receptors on cancer cell surface was successfully achieved for the first time. This fluorescent "OFF-ON" biosensing platform is simple, economical and non-toxic, which can be practically used in biological and medical diagnosis.