Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural s...Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological evaluation.Here,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation strategy.This strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl acceptors.Thus,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully assembled.Immunological evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.展开更多
O-Mannosylation plays a vital role in the regulation of a variety range of biological processes,for instance,brain and muscle development.However,the precise function remains largely unknown due to its innate heteroge...O-Mannosylation plays a vital role in the regulation of a variety range of biological processes,for instance,brain and muscle development.However,the precise function remains largely unknown due to its innate heterogeneity.In this regard,it is still welcome to develop efficient methods to access diverse structurally-defined glycopeptides.In this study,a diversity-oriented assembly of O-mannosylα-dystroglycan(α-DG)glycopeptides has been achieved via a chemoenzymatic strategy.This strategy features(i)gram scale divergent synthesis of core m1,core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation;(i)efficient glycopeptide assembly via the optimized microwave-assisted solid phase peptide synthesis(SPpS);and(ii)enzymatic elaboration of the core glycan structures to install galactosyl and sialyl-galactosyl moieties.The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1,core m2 and core m3 mannosyl glycans,including a core m2 glycopeptide bearing a heptasaccharide for the first time.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.21977063,92053110,and 22177061)the National Key Research and Development Program of China(grant no.2018YFA0902000)+3 种基金the China Postdoctoral Science Foundation(grant no.2020M680090)the Qilu Youth Scholar Program of Shandong University,the Central Government Guide Local Science and Technology Development Funds(grant no.YDZX20203700002579)the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(grant no.2021-RC350-002)the CAMS Innovation Fund for Medical Sciences(CIFMS)(grant no.2021-1-I2M-026).
文摘Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological evaluation.Here,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation strategy.This strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl acceptors.Thus,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully assembled.Immunological evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.
基金This work is financially supported by the National Natural Science Foundation of China(Grant Nos.22177061,92053110,21977063,21907056)the China Postdoctoral Science Foundation(2020M680090)+2 种基金the Shenzhen Science and Technology Program(RCBS20200714114957255)the Open Projects Fund of Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology(2021CCG01&02)the Central Government Guide Local Science and Technology Development Funds(YDZX20203700002579).
文摘O-Mannosylation plays a vital role in the regulation of a variety range of biological processes,for instance,brain and muscle development.However,the precise function remains largely unknown due to its innate heterogeneity.In this regard,it is still welcome to develop efficient methods to access diverse structurally-defined glycopeptides.In this study,a diversity-oriented assembly of O-mannosylα-dystroglycan(α-DG)glycopeptides has been achieved via a chemoenzymatic strategy.This strategy features(i)gram scale divergent synthesis of core m1,core m2 and core m3 mannosylated amino acids from judiciously designed protecting group strategies and chemical glycosidation;(i)efficient glycopeptide assembly via the optimized microwave-assisted solid phase peptide synthesis(SPpS);and(ii)enzymatic elaboration of the core glycan structures to install galactosyl and sialyl-galactosyl moieties.The efficiency and flexibility of this chemoenzymatic approach was demonstrated with the construction of 12 glycopeptides with different core m1,core m2 and core m3 mannosyl glycans,including a core m2 glycopeptide bearing a heptasaccharide for the first time.