Synthesis of methylphosphorylated oligomannosides structurally related to lipopolisaccharide O-antigens of Klebsiella pneumoniae serotype O3 and their application for detection of specific antibodies in rabbit and human sera

Synthesis of methylphosphorylated oligomannosides structurally related to lipopolisaccharide O-antigens of Klebsiella pneumoniae serotype O3 and their application for detection of specific antibodies in rabbit and human sera Научная публикация

Журнал

Organic & Biomolecular Chemistry
ISSN: 1477-0520 , E-ISSN: 1477-0539

Вых. Данные

Год: 2023, Том: 21, Номер: 41, Страницы: 8306-8319 Страниц : 14 DOI: 10.1039/d3ob01203d

Авторы

Solovev Arsenii ¹ , Denisova Evgeniya M. ¹ , Kurbatova Ekaterina A. ^1,2 , Kutsevalova Olga ³ , Boronina Lubov G. ⁴ , Ageevets Vladimir A. ⁵ , Sidorenko Sergey V ⁵ , Krylov Vadim B. ¹ , Nifantiev Nikolay E. ¹

Организации

1	N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russian Federation
2	Laboratory of Immunology, I. I. Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia
3	National Medical Research Center of Oncology, Laboratory of Clinical Microbiology, 14 Liniya Str., 63, 344037 Rostov-on-Don, Russia
4	Ural State Medical University, 3 Repina Str., 620028 Yekaterinburg, Russia
5	Pediatric Research and Clinical Center for Infectious Diseases, 9 Prof. Popov Street, 197022 Saint Petersburg, Russia

Methylphosphorylated mono-, di- and trimannosides structurally related to the lipopolysaccharide (LPS) O-antigens of Klebsiella pneumoniae of serotype O3 were synthesized and conjugated with a biotin tag. The stereo- and regioselective assembly of target carbohydrate chains was conducted using uniform monosaccharide synthetic blocks. After that, a methylphosphate group was introduced by coupling with a methyl-H-phosphonate reagent followed by oxidation and deprotection to give the target oligosaccharides. The 1H and 13C NMR spectra of the obtained compounds showed a good fit with the spectrum of the corresponding natural polysaccharide. The newly prepared biotinylated oligosaccharides along with the previously reported biotinylated glycoconjugates related to galactan I and galactan II of K. pneumoniae LPS were used for the ELISA detection of antibodies in anti-K. pneumoniae rabbit sera. Anti-O3 serum antibodies specifically recognized the synthesized oligosaccharide ligands with terminal methylphosphomannosyl residues, whereas anti-O1 serum antibodies recognized the oligosaccharide related to K. pneumoniae galactan II. The analysis of human sera from patients with confirmed Klebsiella infection also revealed the presence of antibodies against the synthesized oligosaccharides in clinical cases. Thus, the described compounds together with other Klebsiella related antigenic oligosaccharides could be potentially used as molecular probes for K. pneumoniae serological diagnostics development and strain serotyping.

Solovev A. , Denisova E.M. , Kurbatova E.A. , Kutsevalova O. , Boronina L.G. , Ageevets V.A. , Sidorenko S.V. , Krylov V.B. , Nifantiev N.E.
Synthesis of methylphosphorylated oligomannosides structurally related to lipopolisaccharide O-antigens of Klebsiella pneumoniae serotype O3 and their application for detection of specific antibodies in rabbit and human sera
Organic & Biomolecular Chemistry. 2023. V.21. N41. P.8306-8319. DOI: 10.1039/d3ob01203d WOS Scopus OpenAlex

≡ Web of science:	WOS:001078042600001
≡ Scopus:	2-s2.0-85174534454
≡ OpenAlex:	W4387087836