Streptococcus pneumoniae (SP) is a common human pathogen associated with a broad spectrum of diseases and it is still a leading cause of mortality and morbidity worldwide, especially in children. Moreover, SP is increasingly associated with drug resistance. Vaccination against the pathogen may thus represent an important strategy to overcome its threats to human health. In this context, revealing the molecular determinants of SP immunoreactivity may be relevant for the development of novel molecules with therapeutic perspectives as vaccine components. Serogroup 19 comprises the immune-cross reactive types 19F, 19A, 19B and 19C and it accounts for a high percentage of invasive pneumococcal diseases, mainly caused by serotypes 19F and 19A. Herein, we report the synthesis and biological evaluation of an aminopropyl derivative of the trisaccharide repeating unit of SP 19A. We compare two different synthetic strategies, based on different disconnections between the three monosaccharides which make up the final trisaccharide, to define the best approach for the preparation of the trisaccharide. Synthetic accessibility to the trisaccharide repeating unit lays the basis for the development of more complex biopolymer as well as saccharide conjugates. We also evaluate the binding affinity of the trisaccharide for anti-19A and anti-19F sera and discuss the relationship between the chemical properties of the trisaccharide unit and biological activity.

Synthesis and biological evaluation of a trisaccharide repeating unit derivative of Streptococcus pneumoniae 19A capsular polysaccharide / L. Morelli, S. Fallarini, G. Lombardi, C. Colombo, L. Lay, F. Compostella. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 26:21(2018 Nov 15), pp. 5682-5690. [10.1016/j.bmc.2018.10.016]

Synthesis and biological evaluation of a trisaccharide repeating unit derivative of Streptococcus pneumoniae 19A capsular polysaccharide

L. Morelli
Primo
;
C. Colombo;L. Lay
Penultimo
;
F. Compostella
Ultimo
2018

Abstract

Streptococcus pneumoniae (SP) is a common human pathogen associated with a broad spectrum of diseases and it is still a leading cause of mortality and morbidity worldwide, especially in children. Moreover, SP is increasingly associated with drug resistance. Vaccination against the pathogen may thus represent an important strategy to overcome its threats to human health. In this context, revealing the molecular determinants of SP immunoreactivity may be relevant for the development of novel molecules with therapeutic perspectives as vaccine components. Serogroup 19 comprises the immune-cross reactive types 19F, 19A, 19B and 19C and it accounts for a high percentage of invasive pneumococcal diseases, mainly caused by serotypes 19F and 19A. Herein, we report the synthesis and biological evaluation of an aminopropyl derivative of the trisaccharide repeating unit of SP 19A. We compare two different synthetic strategies, based on different disconnections between the three monosaccharides which make up the final trisaccharide, to define the best approach for the preparation of the trisaccharide. Synthetic accessibility to the trisaccharide repeating unit lays the basis for the development of more complex biopolymer as well as saccharide conjugates. We also evaluate the binding affinity of the trisaccharide for anti-19A and anti-19F sera and discuss the relationship between the chemical properties of the trisaccharide unit and biological activity.
No
English
Settore BIO/10 - Biochimica
Articolo
Esperti anonimi
Pubblicazione scientifica
   Nanoplatforms for enhanced immune responses
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2015RNWJAM_002
15-nov-2018
24-ott-2018
Pergamon : Elsevier Science
26
21
5682
5690
9
Pubblicato
Periodico con rilevanza internazionale
crossref
Aderisco
info:eu-repo/semantics/article
Synthesis and biological evaluation of a trisaccharide repeating unit derivative of Streptococcus pneumoniae 19A capsular polysaccharide / L. Morelli, S. Fallarini, G. Lombardi, C. Colombo, L. Lay, F. Compostella. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 26:21(2018 Nov 15), pp. 5682-5690. [10.1016/j.bmc.2018.10.016]
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262
Article (author)
no
L. Morelli, S. Fallarini, G. Lombardi, C. Colombo, L. Lay, F. Compostella
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/597152
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