Structural Diversity Analysis Of Glycosides From Different Biological Sources

Glycosides are widely distributed in natural world,which are formed by the glycosylation of secondary metabolites of animals,plants,fungi and bacteria.The combination of carbohydrate with NPs can greatly enhance the biological activity of NPs because of the access of carbohydrate to a unique chemical space.Compared to synthetic molecules,glycosides are safer,more effective,cheaper,and they are often used in the treatment of various diseases.Therefore,the analysis of glycoside structures in combination with biological sources can promote the human`s understanding of glycosides,which can lead to rapid and accurate screening of glycoside suitable for drug discovery.In order to explore the structural characteristics of natural glycosides,a new glycosyl identification standard was designed in this thesis as a basis for carrying out the analysis of natural glycosides.We analyzed the information on species origin and compound types in the natural product dictionary.With regard to glycosidic molecules of different biological origins,plants had the highest percentage of glycosylation at 25.0%,followed by bacteria(20.8%),animals(8.4%),and fungi(4.5%),respectively.This phenomenon was more pronounced among species classified in different phyla and classes,with the highest percentage of glycosylation in echinoderms(56.1%)and the lowest in molluscs(1.5%).The different compounds types of natural products also affect the percentage of glycosylation,for example,steroids,tannins and flavonoids undergo high percentage of glycosylation,45.2%,44.8% and 39.2%,respectively,while alkaloids,amino acids and oxetane natural products undergo low percentage of glycosylation,5.7%,5.2% and6.4%,respectively.Combining the analysis of species origin and compound types,we found that glycosides such as tannins,flavonoids and lignans were mainly derived from plants,and glycosides such as polyketides and polypyrroles were mainly derived from bacteria.We have analyzed the drug-like properties of natural glycosides.The results showed that glycoside molecules have more potential to become drugs compared to aglycone,and the aglycone of glycosides has more potential to become drugs compared to non-glycosidic molecules.In addition,glycosides produced by animals have more complex structures,better molecular flexibility,and those produced by plants have better aqueous solubility.From the analysis of the scaffolds of aglycone of animal,plant,fungi and bacterial origin,most of them are ternary and more than ternary fused and bridge ring in animals.There are more fused ring scaffolds with low degree of unsaturation in plants,and most of them contain five-and six-membered ring systems with oxygen.The scaffold of bacterial origin contains a large number of N and O heterocycles and have macrocyclic structures among them.Heteroatom-containing scaffolds are not common in fungi,which have unique fused ring and bridge ring with multi-chiral centers as well as unique polyaromatic and anthracyclic scaffold.In this thesis,the substitution sites of glycosyl in glycosides and found that most natural glycosides occurred with single-site substitution(80.2%)and double-site substitution(18.1%),and a few with multi-site substitution.In the single-site substitution pattern,the number of monosaccharide substitutions was larger than that of oligosaccharide substitutions.The number of "monosaccharide-monosaccharide" mode and "monosaccharide-oligosaccharide" mode were comparable in the two-site substitution pattern,and no "oligosaccharide-oligosaccharide" mode was found.In addition,we also analyzed the glycosidic bonds and glycosyl modification types with species information,and found that the distribution of different types of glycosidic bonds varied greatly among species,with S-glycosides being found in large numbers only in plants and bacteria,and O-glycosides,C-glycosides,and N-glycosides being found in all four biological sources.The distribution of different types of glycosyl modifications also varied among species,with O-site alkylation and O-site sulfation modifications predominant in animals,and in plants,bacteria,and fungi,we found that their glycosyl structure modifications were mostly O-site carboxylation and O-site alkylation modifications,while fungi had almost no N-site acylation and O-site phosphorylation modifications.In summary,we have performed a series of cheminformatics analyses of glycosides(glycosides and aglycone)in combination with different species,from which we found that there are obvious structural differences between glycosides of different species origin.The continuous refinement of this information can facilitate our understanding of the structure of natural glycosides and facilitate the discovery of natural glycoside drugs.