PMID- 31482123
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231013
IS  - 2374-7943 (Print)
IS  - 2374-7951 (Electronic)
IS  - 2374-7943 (Linking)
VI  - 5
IP  - 8
DP  - 2019 Aug 28
TI  - Synthetic, Zwitterionic Sp1 Oligosaccharides Adopt a Helical Structure Crucial 
      for Antibody Interaction.
PG  - 1407-1416
LID - 10.1021/acscentsci.9b00454 [doi]
AB  - The zwitterionic Streptococcus pneumoniae serotype 1 polysaccharide (Sp1) is an 
      important anchor point for our immune system to act against streptococcal 
      infections. Antibodies can recognize Sp1 saccharides, and it has been postulated 
      that Sp1 can elicit a T-cell-dependent immune reaction as it can be presented by 
      MHC-II molecules. To unravel the molecular mode of action of this unique 
      polysaccharide we here describe the chemical synthesis of a set of Sp1 fragments, 
      ranging from 3 to 12 monosaccharides in length. We outline a unique synthetic 
      approach to overcome the major synthetic challenges associated with the complex 
      Sp1 structure and provide a stereoselective route of synthesis for the 
      oligosaccharide backbone as well as a strategy to introduce the carboxylic acid 
      functions. Molecular dynamics (MD) simulations together with NMR spectroscopy 
      studies reveal that the oligosaccharides take up helical structures with the 
      nona- and dodecasaccharide completing a full helical turn. The 3D structure of 
      the oligosaccharides coincides with the topology required for good interaction 
      with anti-Sp1 antibodies, which has been mapped in detail using STD-NMR. Our 
      study has revealed the Sp1 nona- and dodecasaccharides as promising synthetic 
      antigens, displaying all (3D) structural elements required to mimic the natural 
      polysaccharide and required to unravel the molecular mode of action of these 
      unique zwitterionic polysaccharides.
FAU - Zhang, Qingju
AU  - Zhang Q
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
AD  - The National Research Centre for Carbohydrate Synthesis, Jiangxi Normal 
      University, No 99 Ziyang Avenue, Nanchang 330022, China.
FAU - Gimeno, Ana
AU  - Gimeno A
AD  - CIC bioGUNE, Bizkaia Technology Park, Building 801 A, 48170 Derio, Spain.
FAU - Santana, Darielys
AU  - Santana D
AD  - Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
FAU - Valdes-Balbin, Yury
AU  - Valdes-Balbin Y
AD  - Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba.
FAU - Rodriguez-Noda, Laura M
AU  - Rodriguez-Noda LM
AD  - Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba.
FAU - Hansen, Thomas
AU  - Hansen T
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
FAU - Kong, Li
AU  - Kong L
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
FAU - Shen, Mengjie
AU  - Shen M
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
FAU - Overkleeft, Herman S
AU  - Overkleeft HS
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
FAU - Verez-Bencomo, Vicente
AU  - Verez-Bencomo V
AD  - Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba.
FAU - van der Marel, Gijsbert A
AU  - van der Marel GA
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
FAU - Jimenez-Barbero, Jesus
AU  - Jimenez-Barbero J
AD  - CIC bioGUNE, Bizkaia Technology Park, Building 801 A, 48170 Derio, Spain.
AD  - Ikerbasque, Basque Foundation for Science, Maria Diaz de Haro 3, Bilbao, 48013 
      Bizkaia, Spain.
AD  - Department of Organic Chemistry II, Faculty of Science and Technology, University 
      of the Basque Country, EHU-UPV, 48940 Leioa, Spain.
FAU - Chiodo, Fabrizio
AU  - Chiodo F
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
AD  - Amsterdam Infection and Immunity Institute, Department of Molecular Cell Biology 
      and Immunology, Amsterdam UMC, Location VUmc, 1007 MB Amsterdam, The Netherlands.
FAU - Codee, Jeroen D C
AU  - Codee JDC
AD  - Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, 
      The Netherlands.
LA  - eng
PT  - Journal Article
DEP - 20190724
PL  - United States
TA  - ACS Cent Sci
JT  - ACS central science
JID - 101660035
PMC - PMC6716135
COIS- The authors declare no competing financial interest.
EDAT- 2019/09/05 06:00
MHDA- 2019/09/05 06:01
PMCR- 2019/07/24
CRDT- 2019/09/05 06:00
PHST- 2019/05/07 00:00 [received]
PHST- 2019/09/05 06:00 [entrez]
PHST- 2019/09/05 06:00 [pubmed]
PHST- 2019/09/05 06:01 [medline]
PHST- 2019/07/24 00:00 [pmc-release]
AID - 10.1021/acscentsci.9b00454 [doi]
PST - ppublish
SO  - ACS Cent Sci. 2019 Aug 28;5(8):1407-1416. doi: 10.1021/acscentsci.9b00454. Epub 
      2019 Jul 24.