Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis

Zhihao Li; Teodora Bavaro; Sara Tengattini; Roberta Bernardini; Maurizio Mattei; Francesca Annunziata; Richard B Cole; Changping Zheng; Matthieu Sollogoub; Lucia Tamborini; Marco Terreni; Yongmin Zhang

doi:10.1016/j.ejmech.2020.112578

Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis

Eur J Med Chem. 2020 Oct 15:204:112578. doi: 10.1016/j.ejmech.2020.112578. Epub 2020 Jul 15.

Authors

Affiliations

¹ Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France.
² Drug Sciences Department, University of Pavia, Viale Taramelli 12, 27100, Pavia, Italy.
³ Italy Centro Servizi Interdipartimentale - STA, University of Rome "Tor Vergata", Rome, Italy.
⁴ Italy Centro Servizi Interdipartimentale - STA, University of Rome "Tor Vergata", Rome, Italy; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
⁵ Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133, Milan, Italy.
⁶ Drug Sciences Department, University of Pavia, Viale Taramelli 12, 27100, Pavia, Italy. Electronic address: marco.terreni@unipv.it.
⁷ Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry & Chemical Engineering, Hainan Normal University, Haikou 571158, China. Electronic address: yongmin.zhang@upmc.fr.

PMID: 32717482
DOI: 10.1016/j.ejmech.2020.112578

Abstract

Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.

Keywords: Chemoenzymatic synthesis; Glycoconjugate; Lipoarabinomannan; Tuberculosis; Vaccine.

MeSH terms

Bacterial Vaccines / chemical synthesis*
Bacterial Vaccines / chemistry
Bacterial Vaccines / pharmacology*
Drug Design
Glycoconjugates / chemical synthesis*
Glycoconjugates / chemistry
Glycoconjugates / pharmacology*
Glycosylation
Humans
Mannans / chemistry*
Tuberculosis / prevention & control*

Substances

Bacterial Vaccines
Glycoconjugates
Mannans
arabinomannan