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21 results on '"Huo, Chang‐Xin"'

2. Expedient Synthesis of a Library of Heparan Sulfate‐Like “Head‐to‐Tail” Linked Multimers for Structure and Activity Relationship Studies**

Author

Zhang, Jicheng, primary, Liang, Li, additional, Yang, Weizhun, additional, Ramadan, Sherif, additional, Baryal, Kedar, additional, Huo, Chang‐Xin, additional, Bernard, Jamie J., additional, Liu, Jian, additional, Hsieh‐Wilson, Linda, additional, Zhang, Fuming, additional, Linhardt, Robert J., additional, and Huang, Xuefei, additional

Published
2022
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3. Expedient Synthesis of a Library of Heparan Sulfate Like “Head to Tail” Linked Multimers for Structure and Activity Relationship Studies

Author

Zhang, Jicheng, Liang, Li, Yang, Weizhun, Ramadan, Sherif, Baryal, Kedar, Huo, Chang-Xin, Bernard, Jamie J., Liu, Jian, Hsieh-Wilson, Linda, Zhang, Fuming, Linhardt, Robert J., Huang, Xuefei, Zhang, Jicheng, Liang, Li, Yang, Weizhun, Ramadan, Sherif, Baryal, Kedar, Huo, Chang-Xin, Bernard, Jamie J., Liu, Jian, Hsieh-Wilson, Linda, Zhang, Fuming, Linhardt, Robert J., and Huang, Xuefei

Abstract

Heparan sulfate (HS) plays significant roles in various biological processes such as inflammation, cell proliferation, and bacterial and viral infection. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of the relationship between their diverse structures and biological functions. While HS syntheses have advanced significantly in recent years, preparation of HS libraries remains a tremendous challenge due to the difficulties in achieving high yields in glycosylation and sulfation reactions especially with longer glycans and the need to prepare multiple compounds. A new strategy to synthesize a library of HS-like pseudo-hexasaccharides has been developed to expedite library preparation. HS disaccharides were linked in a “head-to-tail” fashion from the reducing end of a module to the non-reducing end of a neighboring module to mimic native HS. Three differentially sulfated HS disaccharides were designed and prepared from a common intermediate. Conjugation of these modules using amide chemistry bypassed the need for challenging glycosylation reactions to extend the HS backbone. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved using these three HS modules. This new class of compounds mimicked well the native HS with their binding to fibroblast growth factor 2 (FGF-2) exhibiting similar structure-activity relationship trends as HS hexasaccharides. The ease of synthesis and the ability to mimic natural HS suggest the new head-to-tail linked pseudo-hexasaccharides could be an exciting tool to facilitate the understanding of HS biology.

Published
2022

5. Chemical Synthesis and Immunological Evaluation of Pertussis-Like Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti-pertussis Vaccine

Author

Wang, Peng, Huo, Chang-xin, Lang, Shuyao, Caution, Kyle, Nick, Setare Tahmasebi, Dubey, Purnima, Deora, Rajendar, and Huang, Xuefei

Subjects
Lipopolysaccharides, Pertussis Vaccine, Mice, Immunoglobulin G, Hemocyanins, Animals, Oligosaccharides, Cattle, Enzyme-Linked Immunosorbent Assay, Serum Albumin, Bovine, Article, Fucose
Abstract

The 60-year high Bordetella pertussis (B. pertussis) infection rate in the world suggests the urgent need for new anti-pertussis vaccines. Lipopolysaccharide (LPS) of B. pertussis is an attractive antigen for vaccine development. With the presence of multiple rare sugars and unusual glycosyl linkages, B. pertussis LPS is a highly challenging synthetic target. In this work, aided by molecular dynamics simulation and modeling, the pertussis LPS like pentasaccharide was chemically synthesized for the first time. The pentasaccharide was conjugated with a powerful carrier, bacteriophage Qβ as a vaccine candidate. Immunization of mice with the conjugate induced robust anti-glycan IgG responses with IgG titers reaching several million enzyme-linked immunosorbent assay (ELISA) units. The antibodies generated were long lasting and boostable, and could recognize multiple clinical strains of B. pertussis, highlighting the potential of Qβ-glycan as a new anti-pertussis vaccine.

Published
2020

6. Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development

Author

Wang, Hexiang, primary, Ren, Bo, additional, Liu, Ye, additional, Jiang, Beibei, additional, Guo, Yin, additional, Wei, Min, additional, Luo, Lusong, additional, Kuang, Xianzhao, additional, Qiu, Ming, additional, Lv, Lei, additional, Xu, Hong, additional, Qi, Ruipeng, additional, Yan, Huibin, additional, Xu, Dexu, additional, Wang, Zhiwei, additional, Huo, Chang-Xin, additional, Zhu, Yutong, additional, Zhao, Yuan, additional, Wu, Yiyuan, additional, Qin, Zhen, additional, Su, Dan, additional, Tang, Tristin, additional, Wang, Fan, additional, Sun, Xuebing, additional, Feng, Yingcai, additional, Peng, Hao, additional, Wang, Xing, additional, Gao, Yajuan, additional, Liu, Yong, additional, Gong, Wenfeng, additional, Yu, Fenglong, additional, Liu, Xuesong, additional, Wang, Lai, additional, and Zhou, Changyou, additional

Published
2020
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9. Streamlined synthesis of core disaccharide building blocks from natural polysaccharides for the generation of heparan sulfate libraries

Author

Pawar, Nitin Jalindar, Wang, Lei, Higo, Takuya, Bhattacharya, Chandrabali, Kancharla, Pavan K., Zhang, Fuming, Baryal, Kedar, Huo, Chang-Xin, Liu, Jian, Linhardt, Robert J., Huang, Xuefei, Hsieh-Wilson, Linda C., Pawar, Nitin Jalindar, Wang, Lei, Higo, Takuya, Bhattacharya, Chandrabali, Kancharla, Pavan K., Zhang, Fuming, Baryal, Kedar, Huo, Chang-Xin, Liu, Jian, Linhardt, Robert J., Huang, Xuefei, and Hsieh-Wilson, Linda C.

Abstract

Heparan sulfate (HS) glycosaminoglycans (GAGs) are linear, diversely sulfated polysaccharides that regulate a wide range of essential biol. processes, including growth factor signaling, blood coagulation, viral infection, neural development, and cancer. HS chains consist of repeating disaccharide units of glucosamine (GlcN) joined via a-1,4-linkages to either D-glucuronic acid (GlcA) or L-iduronic acid (IdoA). Sulfation at the 3-O-, 6-O-, and N-positions of GlcN and the 2-O-position of IdoA or GlcA creates many different sulfation sequences that are tightly regulated in vivo. The diverse biol. functions of HS GAGs are thought to stem from their complex sulfation patterns. However, understanding their structure-activity relationships (SAR) has been hampered by a lack of methods to synthesize large collections of HS oligosaccharides with defined sulfation sequences. A major obstacle is the prepn. of differentially protected disaccharide building blocks, which typically require 20-30 chem. steps. Here, we report a new approach to access all four of the core disaccharides required for HS assembly from natural heparin and heparosan (K5) polysaccharides. The use of disaccharides rather than monosaccharides as minimal synthetic precursors greatly accelerates the synthesis of HS GAGs, providing easier access to core building blocks for the assembly of strategically protected HS tetrasaccharides in significantly fewer steps. Rapid access to such building blocks promises to significantly expand the scope of HS synthesis, enabling the future generation of large libraries of compds. for detailed investigations into the 'sulfation code' and its roles in biol.

Published
2019

10. Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly

Author

Pawar, Nitin J., primary, Wang, Lei, additional, Higo, Takuya, additional, Bhattacharya, Chandrabali, additional, Kancharla, Pavan K., additional, Zhang, Fuming, additional, Baryal, Kedar, additional, Huo, Chang‐Xin, additional, Liu, Jian, additional, Linhardt, Robert J., additional, Huang, Xuefei, additional, and Hsieh‐Wilson, Linda C., additional

Published
2019
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19. Expedient Synthesis of a Library of Heparan Sulfate-Like "Head-to-Tail" Linked Multimers for Structure and Activity Relationship Studies.

Author

Zhang J, Liang L, Yang W, Ramadan S, Baryal K, Huo CX, Bernard JJ, Liu J, Hsieh-Wilson L, Zhang F, Linhardt RJ, and Huang X

Subjects
Oligosaccharides chemistry, Structure-Activity Relationship, Protein Binding, Heparitin Sulfate chemistry, Disaccharides chemistry
Abstract

Heparan sulfate (HS) plays important roles in many biological processes. The inherent complexity of naturally existing HS has severely hindered the thorough understanding of their structure-activity relationship. To facilitate biological studies, a new strategy has been developed to synthesize a HS-like pseudo-hexasaccharide library, where HS disaccharides were linked in a "head-to-tail" fashion from the reducing end of a disaccharide module to the non-reducing end of a neighboring module. Combinatorial syntheses of 27 HS-like pseudo-hexasaccharides were achieved. This new class of compounds bound with fibroblast growth factor 2 (FGF-2) with similar structure-activity trends as HS oligosaccharides bearing native glycosyl linkages. The ease of synthesis and the ability to mirror natural HS activity trends suggest that the new head-to-tail linked pseudo-oligosaccharides could be an exciting tool to facilitate the understanding of HS biology., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Published
2022
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20. Syntheses of Salmonella Paratyphi A Associated Oligosaccharide Antigens and Development towards Anti-Paratyphoid Fever Vaccines.

Author

Dhara D, Baliban SM, Huo CX, Rashidijahanabad Z, Sears KT, Nick ST, Misra AK, Tennant SM, and Huang X

Subjects
Animals, Antibodies, Bacterial immunology, Antigens, Bacterial immunology, Mice, Vaccines, Synthetic, Oligosaccharides immunology, Paratyphoid Fever prevention & control, Salmonella paratyphi A immunology, Typhoid-Paratyphoid Vaccines administration & dosage, Typhoid-Paratyphoid Vaccines chemistry
Abstract

With the emergence of multidrug resistant Salmonella strains, the development of anti-Salmonella vaccines is an important task. Currently there are no approved vaccines against Salmonella Paratyphi A, the leading cause of paratyphoid fever. To fill this gap, oligosaccharides corresponding to the O-polysaccharide repeating units from the surface of Salmonella Paratyphi A have been synthesized through convergent stereoselective glycosylations. The synthetic glycan antigen was conjugated with a powerful immunogenic carrier system, the bacteriophage Qβ. The resulting construct was able to elicit strong and long-lasting anti-glycan IgG antibody responses, which were highly selective toward Salmonella Paratyphi A associated glycans. The availability of well-defined glycan antigen enabled the determination that one repeating unit of the polysaccharide is sufficient to induce protective antibodies, and the paratose residue and/or the O-acetyl modifications on the backbone are important for recognition by antibodies elicited by a Qβ-tetrasaccharide conjugate. Immune sera provided excellent protection to mice from lethal challenge with Salmonella Paratyphi A, highlighting the potential of the synthetic glycan-based vaccine., (© 2020 Wiley-VCH GmbH.)

Published
2020
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21. [Recent advance in carbohydrate-based cancer vaccines].

Author

Huo CX and Ye XS

Subjects
Animals, Antigens, Tumor-Associated, Carbohydrate immunology, Cancer Vaccines chemistry, Cancer Vaccines immunology, Cancer Vaccines therapeutic use, Carbohydrates chemistry, Carbohydrates immunology, Epitopes, T-Lymphocyte chemistry, Epitopes, T-Lymphocyte immunology, Glycoconjugates immunology, Humans, Immune Tolerance, Metabolic Engineering methods, Neoplasms therapy, Oligosaccharides chemistry, Antigens, Tumor-Associated, Carbohydrate chemistry, Cancer Vaccines chemical synthesis, Glycoconjugates chemistry, Neoplasms prevention & control
Abstract

The abnormal glycans expressing on the surface of tumor cells are good targets to develop carbohydrate-based anti-cancer vaccines. However, one of the major problems is that carbohydrate antigens possess weak immunogenicity. This review summarizes the recent efforts to overcome this problem: glycoconjugates produced by coupling the carbohydrate antigens and proper carrier proteins improve their immunogenicity, many glycoconjugates have entered clinical trials; the vaccines become chemically well-defined when coupling the carbohydrate antigens with a T-cell peptide epitope and an immunostimulant to form fully synthetic multi-component glycoconjugate vaccines; the modification of carbohydrate antigens in combination with the technology of metabolic oligosaccharide engineering of tumor cells induces a strong immune response; and the fact that the antibodies elicited against the unnatural carbohydrate antigens can recognize the native carbohydrate antigens on tumor cells provides a new promising strategy for the development of anti-cancer vaccines.

Published
2012

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