title: α-Glycosylation by D-glucosamine-derived donors: synthesis of heparosan and heparin analogues that interact with mycobacterial heparin-binding hemagglutinin.
abstract: Numerous biomolecules possess α-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted β-isomer. We report herein a versatile approach in affording full α-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.
authors.affiliation: Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei 115, Taiwan.
authors.forename: Medel Manuel L
authors.initials: MM
authors.lastname: Zulueta
authors.forename: Shu-Yi
authors.initials: SY
authors.lastname: Lin
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Lin
authors.forename: Ching-Jui
authors.initials: CJ
authors.lastname: Huang
authors.forename: Chun-Chih
authors.initials: CC
authors.lastname: Wang
authors.forename: Chiao-Chu
authors.initials: CC
authors.lastname: Ku
authors.forename: Zhonghao
authors.initials: Z
authors.lastname: Shi
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chyan
authors.forename: Deli
authors.initials: D
authors.lastname: Irene
authors.forename: Liang-Hin
authors.initials: LH
authors.lastname: Lim
authors.forename: Tsung-I
authors.initials: TI
authors.lastname: Tsai
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Hu
authors.forename: Susan D
authors.initials: SD
authors.lastname: Arco
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
authors.forename: Shang-Cheng
authors.initials: SC
authors.lastname: Hung
mesh_terms: D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D005944:Glucosamine / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006493:Heparin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism; D037102:Lectins / Q000737:chemistry / Q000378:metabolism*; D009169:Mycobacterium tuberculosis; D010446:Peptide Fragments / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D004187:Disaccharides; D037102:Lectins; D010446:Peptide Fragments; C104578:heparin-binding hemagglutinin; C560363:heparosan; D006493:Heparin; D005944:Glucosamine