Chemical synthesis and antibody affinity of epitope fragments from <i>Helicobacter pylori</i> lipopolysaccharide

ZHAO Hui; ZOU Xiaopeng; XIAO Lei; HU Jing; YIN Jian

doi:10.11665/j.issn.1000-5048.2024031201

Journal of China Pharmaceutical University > 2024 > 55(5): 645-656. > DOI: 10.11665/j.issn.1000-5048.2024031201

ZHAO Hui, ZOU Xiaopeng, XIAO Lei, et al. Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide[J]. J China Pharm Univ, 2024, 55(5): 645 − 656. DOI: 10.11665/j.issn.1000-5048.2024031201

Citation:

PDF (1135 KB)

Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide

ZHAO Hui^{1, #},
ZOU Xiaopeng^{1, #},
XIAO Lei¹,
HU Jing^2, ,,
YIN Jian^{1, 3, ,}

1.
Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), School of Biotechnology, Jiangnan University, Wuxi 214122
2.
Wuxi School of Medicine, Jiangnan University, Wuxi 214122
3.
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 22207042, No. 22177041, No. 22277042, No. 22325803)；and the Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology (Ministry of Education), Jiangnan University (No. KLCCB-KF202203)

More Information

Received Date: March 11, 2024

Graphical Abstract

Abstract

Abstract

Helicobacter pylori (Hp) is responsible for chronic gastritis, peptic ulcers, and even gastric cancers. Currently, there is no vaccine to prevent or treat Hp infections. Here, we described the chemical synthesis of α-1,6-glucans with different lengths (di- to hexasaccharide), which are present in the core oligosaccharide of Hp lipopolysaccharide (LPS). The 1,2-cis-glucosidic bonds were constructed successfully using a synergistic glycosylation strategy based on acyl remote participation and solvent effects. The results of glycan microarrays indicated that all synthesized α-1,6-glucan fragments possessed a strong binding to IgG antibodies in both rabbit serum immunized with Hp O1 LPS and patient serum infected with Hp. The α-1,6-linked trisaccharide exhibited strong binding affinity to anti-LPS rabbit IgG antibodies. The α-1,6-glucan trisaccharide and pentasaccharide elicited a strong response to IgG antibodies in sera of most Hp-infected patients. Some patients’ sera exhibited strong binding activity with α-1,6-linked disaccharide. The results suggest that the α-1,6-glucan disaccharide, trisaccharide and pentasaccharide could be important carbohydrate antigen fragments in Hp lipopolysaccharide.
- Helicobacter pylori,
- lipopolysaccharide,
- α-1,6-glucan,
- glycan microarray,
- antibody affinity

FullText(HTML)

References (38)

References

[1]	Xu DY, Zhao SS, Dou J, et al. Engineered endolysin-based “artilysins” for controlling the gram-negative pathogen Helicobacter pylori[J]. AMB Express, 2021, 11(1): 63. doi: 10.1186/s13568-021-01222-8
[2]	Xu WT, Xu LM, Xu CF. Relationship between Helicobacter pylori infection and gastrointestinal microecology[J]. Front Cell Infect Microbiol, 2022, 12: 938608. doi: 10.3389/fcimb.2022.938608
[3]	Reyes VE. Helicobacter pylori and its role in gastric cancer[J]. Microorganisms, 2023, 11(5): 1312. doi: 10.3390/microorganisms11051312
[4]	Lee YC, Dore MP, Graham DY. Diagnosis and treatment of Helicobacter pylori infection[J]. Annu Rev Med, 2022, 73: 183-195. doi: 10.1146/annurev-med-042220-020814
[5]	Abdullah M, Greenfield LK, Bronte-Tinkew D, et al. VacA promotes CagA accumulation in gastric epithelial cells during Helicobacter pylori infection[J]. Sci Rep, 2019, 9(1): 38. doi: 10.1038/s41598-018-37095-4
[6]	Shang Y, Zhao LY, Lu JK. Relationship between inflammatory cytokines and gastric cancer[J]. J China Pharm Univ (中国药科大学学报), 2015, 46(1): 123-128.
[7]	Lunn RM, Mehta SS, Jahnke GD, et al. Cancer hazard evaluations for contemporary needs: highlights from new national toxicology program evaluations and methodological advancements[J]. J Natl Cancer Inst, 2022, 114(11): 1441-1448. doi: 10.1093/jnci/djac164
[8]	Graham DY. Transitioning of Helicobacter pylori therapy from trial and error to antimicrobial stewardship[J]. Antibiotics, 2020, 9(10): 671. doi: 10.3390/antibiotics9100671
[9]	Matos R, Taillieu E, De Bruyckere S, et al. Presence of Helicobacter species in gastric mucosa of human patients and outcome of Helicobacter eradication treatment[J]. J Pers Med, 2022, 12(2): 181. doi: 10.3390/jpm12020181
[10]	Jearth V, Rath MM, Chatterjee A, et al. Drug-resistant Helicobacter pylori: diagnosis and evidence-based approach[J]. Diagnostics, 2023, 13(18): 2944. doi: 10.3390/diagnostics13182944
[11]	Dascălu RI, Bolocan A, Păduaru DN, et al. Multidrug resistance in Helicobacter pylori infection[J]. Front Microbiol, 2023, 14: 1128497. doi: 10.3389/fmicb.2023.1128497
[12]	Imoto I, Yasuma T, D’Alessandro-Gabazza CN, et al. Antimicrobial effects of lactoferrin against Helicobacter pylori infection[J]. Pathogens, 2023, 12(4): 599. doi: 10.3390/pathogens12040599
[13]	Dieye Y, Nguer CM, Thiam F, et al. Recombinant Helicobacter pylori vaccine delivery vehicle: a promising tool to treat infections and combat antimicrobial resistance[J]. Antibiotics, 2022, 11(12): 1701. doi: 10.3390/antibiotics11121701
[14]	Xu XD, Ruan QP, Wu WT. Cloning of UreB from Helicobacter pylori and its expression in E. coli[J]. J China Pharm Univ (中国药科大学学报), 2004, 35(2): 183-186.
[15]	Friedrich V, Gerhard M. Vaccination against Helicobacter pylori - An approach for cancer prevention[J]? Mol Aspects Med, 2023, 92: 101183.
[16]	Dos Santos Viana I, Cordeiro Santos ML, Santos Marques H, et al. Vaccine development against Helicobacter pylori: from ideal antigens to the current landscape[J]. Expert Rev Vaccines, 2021, 20(8): 989-999. doi: 10.1080/14760584.2021.1945450
[17]	Zeng M, Mao XH, Li JX, et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet, 2015, 386(10002): 1457-1464. doi: 10.1016/S0140-6736(15)60310-5
[18]	Zhao Y, Arce-Gorvel V, Conde-Álvarez R, et al. Vaccine development targeting lipopolysaccharide structure modification[J]. Microbes Infect, 2018, 20(9/10): 455-460.
[19]	Hulbert SW, Desai P, Jewett MC, et al. Glycovaccinology: the design and engineering of carbohydrate-based vaccine components[J]. Biotechnol Adv, 2023, 68: 108234. doi: 10.1016/j.biotechadv.2023.108234
[20]	Nishat S, Andreana PR. Entirely carbohydrate-based vaccines: an emerging field for specific and selective immune responses[J]. Vaccines, 2016, 4(2): 19. doi: 10.3390/vaccines4020019
[21]	Feng SJ, Xiong CH, Wang GR, et al. Exploration of recombinant fusion proteins YAPO and YAPL as carrier proteins for glycoconjugate vaccine design against Streptococcus pneumoniae infection[J]. ACS Infect Dis, 2020, 6(8): 2181-2191. doi: 10.1021/acsinfecdis.0c00260
[22]	Meena J, Kumar R, Singh M, et al. Modulation of immune response and enhanced clearance of Salmonella typhi by delivery of Vi polysaccharide conjugate using PLA nanoparticles[J]. Eur J Pharm Biopharm, 2020, 152: 270-281. doi: 10.1016/j.ejpb.2020.05.023
[23]	Qin CJ, Xiong DC, Yin J. Development of carbohydrate-based drugs driven by chemical glycobiology[J]. J China Pharm Univ (中国药科大学学报), 2024, 55(4): 429-431. doi: 10.11665/j.issn.1000-5048.2024071002 Qin CJ, Xiong DC, Yin J. Development of carbohydrate-based drugs driven by chemical glycobiology[J]. J China Pharm Univ (中国药科大学学报), 2024, 55(4): 429-431. doi: 10.11665/j.issn.1000-5048.2024071002
[24]	Qin CJ, Tian GZ, Hu J, et al. Recent chemical synthesis and immunological evaluation of glycans related to bacterial lipopolysaccharides[J]. Curr Opin Chem Biol, 2024, 78: 102424. doi: 10.1016/j.cbpa.2023.102424
[25]	Del Bino L, Østerlid KE, Wu DY, et al. Synthetic glycans to improve current glycoconjugate vaccines and fight antimicrobial resistance[J]. Chem Rev, 2022, 122(20): 15672-15716. doi: 10.1021/acs.chemrev.2c00021
[26]	Sabnis A, Edwards AM. Lipopolysaccharide as an antibiotic target[J]. Biochim Biophys Acta Mol Cell Res, 2023, 1870(7): 119507. doi: 10.1016/j.bbamcr.2023.119507
[27]	Britton S, Papp-Szabo E, Simala-Grant J, et al. A novel Helicobacter pylori cell-surface polysaccharide[J]. Carbohydr Res, 2005, 340(9): 1605-1611. doi: 10.1016/j.carres.2005.04.008
[28]	Monteiro MA, Britton S, Applebee LA, et al. Synthesis and immunogenicity of a Helicobacter pylori lipopolysaccharide-based conjugate[J]. Vaccine, 2011, 29(17): 3098-3102. doi: 10.1016/j.vaccine.2011.02.063
[29]	Harrison BA, Fernández H, Chandan V, et al. Characterization and functional activity of murine monoclonal antibodies specific for α1, 6-glucan chain of Helicobacter pylori lipopolysaccharide[J]. Helicobacter, 2011, 16(6): 459-467. doi: 10.1111/j.1523-5378.2011.00860.x
[30]	Altman E, Chandan V, Harrison BA, et al. Chemoenzymatic synthesis of an α-1, 6-glucan-based conjugate vaccine against Helicobacter pylori[J]. Glycobiology, 2022, 32(8): 691-700. doi: 10.1093/glycob/cwac023
[31]	Zou XP, Hu J, Zhao M, et al. Chemical synthesis of the highly sterically hindered core undecasaccharide of Helicobacter pylori lipopolysaccharide for antigenicity evaluation with human serum[J]. J Am Chem Soc, 2022, 144(32): 14535-14547. doi: 10.1021/jacs.2c03068
[32]	Zhao QP, Zhang H, Zhang YX, et al. Stereoselective synthesis of a branched α-decaglucan[J]. Org Biomol Chem, 2020, 18(33): 6549-6557. doi: 10.1039/D0OB01402H
[33]	Komarova BS, Tsvetkov YE, Pier GB, et al. First synthesis of pentasaccharide glycoform I of the outer core region of the Pseudomonas aeruginosa lipopolysaccharide[J]. J Org Chem, 2008, 73(21): 8411-8421. doi: 10.1021/jo801561p
[34]	Zhang YQ, He HQ, Chen ZX, et al. Merging reagent modulation and remote anchimeric assistance for glycosylation: highly stereoselective synthesis of α-glycans up to a 30-mer[J]. Angew Chem Int Ed Engl, 2021, 60(22): 12597-12606. doi: 10.1002/anie.202103826
[35]	Zou XP, Qin CJ, Pereira CL, et al. Synergistic glycosylation as key to the chemical synthesis of an outer core octasaccharide of Helicobacter pylori[J]. Chemistry, 2018, 24(12): 2868-2872. doi: 10.1002/chem.201800049
[36]	Zhao M, Tian GZ, Qin CJ, et al. Immunological exploration of Helicobacter pylori serotype O₂ O-antigen by using a synthetic glycan library[J]. Chin J Chem, 2024, 42(3): 243-251. doi: 10.1002/cjoc.202300510
[37]	Tian GZ, Hu J, Qin CJ, et al. Chemical synthesis and immunological evaluation of Helicobacter pylori serotype O6 tridecasaccharide O-antigen containing a dd-heptoglycan[J]. Angew Chem Int Ed, 2020, 59(32): 13362-13370. doi: 10.1002/anie.202004267
[38]	Ishiwata A, Tanaka K, Ao JM, et al. Recent advances in stereoselective 1, 2-cis-O-glycosylations[J]. Front Chem, 2022, 10: 972429. doi: 10.3389/fchem.2022.972429

[1]	ZENG Hao, WU Guozhen, ZOU Wuxin, WANG Zhe, SONG Jianfei, SHI Hui, WANG Xiaojian, HOU Tingjun, DENG Yafeng. Optimization of Menin inhibitors based on artificial intelligence-driven molecular factory technology[J]. Journal of China Pharmaceutical University, 2024, 55(3): 326-334. DOI: 10.11665/j.issn.1000-5048.2024040904
[2]	ZHU Yinxue, WANG Dexiang, KONG Ying, LU Wenjie, YE Hui, HAO Haiping. Genetic incorporation of unnatural amino acids into proteins and its translational application in biomedicine[J]. Journal of China Pharmaceutical University, 2022, 53(4): 383-391. DOI: 10.11665/j.issn.1000-5048.20220401
[3]	LI Hui, WEN Shuping, HONG Wenrong. Construction of carbamoyltobramcin-producing engineering S.tenebrarius by disruption of aprK gene[J]. Journal of China Pharmaceutical University, 2013, 44(4): 368-373. DOI: 10.11665/j.issn.1000-5048.20130416
[4]	Molecular method for the identification of Bulbus Fritillariae Cirrhosae[J]. Journal of China Pharmaceutical University, 2010, 41(3): 226-230.
[5]	Study on Microwave-assisted Extraction of Active Constituents in Radix Puerariae[J]. Journal of China Pharmaceutical University, 2002, (5): 26-29.
[6]	Fermentation Conditions for High Level Expression of Novel Human Calcitonin Analogue Gene in Engineering Strain[J]. Journal of China Pharmaceutical University, 2000, (2): 74-77.
[7]	ConstitutiveHigh-Expression of the N-Acetylneuraminate Lyase Gene of Escherichia coli[J]. Journal of China Pharmaceutical University, 2000, (1): 68-71.
[8]	Molecular Cloning and Expression of Tryptophanase Gene of Escherichia coli[J]. Journal of China Pharmaceutical University, 1999, (2): 61-64.
[9]	Determination of Molecular Weight of Chitosan by High Performance Gel Permeation Chromatography[J]. Journal of China Pharmaceutical University, 1994, (4): 53-55.
[10]	Molecular Mechanics and Molecular Pharmacology of Cholinergic and Cholinolytic Drugs[J]. Journal of China Pharmaceutical University, 1993, (6): 363-370.

Cited By

Get Citation

PDF

XML

Article views (75) PDF downloads (23)

Turn off MathJax

Article Contents

Abstract

References

Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide

Abstract

References

Related Articles

Catalog

Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide

Abstract

References

Related Articles

Catalog

Export File

Citation

Format

Content