Advanced

Synthesis of sialic acid analoges for investigation of antagonistic activity against bacterial sialic acid transporters

Warlin, Niklas LU and Furevi, Axel LU (2016) KOK820 20161
Department of Chemistry
Centre for Analysis and Synthesis
Abstract
Sialic acids are monosaccharides commonly located towards the end of the glycans in the human cell membrane. Therefore, sialic acids are in direct contact with the surroundings of the cell and are important antigens involved in the identification of human cells for the immune system. Some pathogenic bacteria have developed mechanisms for absorbing this sugar, and can use it to glycosylate their lipopolysaccharides, masking them from the human immune system. As this mechanism is essential for the survival of the bacteria in the human host, preventing it may result in a new mechanism of action for antibiotics.
By synthesizing sialic acid analogues and later testing their affinity for the sialic acid membrane protein - a sodium solute... (More)
Sialic acids are monosaccharides commonly located towards the end of the glycans in the human cell membrane. Therefore, sialic acids are in direct contact with the surroundings of the cell and are important antigens involved in the identification of human cells for the immune system. Some pathogenic bacteria have developed mechanisms for absorbing this sugar, and can use it to glycosylate their lipopolysaccharides, masking them from the human immune system. As this mechanism is essential for the survival of the bacteria in the human host, preventing it may result in a new mechanism of action for antibiotics.
By synthesizing sialic acid analogues and later testing their affinity for the sialic acid membrane protein - a sodium solute symporter (SSS) protein, new sialic acid derivatives with stronger affinity towards the active site could be constructed. We have been focusing on the synthesis of thiosialic acid derivatives of α and β stereoisomers for the sialic acid Neu5Ac, as well as different amides in the C5 position. A synthetic pathway for modifications at position C3 is also suggested.
The affinity for the smallest of the β-thiosialic acid, 2-thioethyl-5-acetamido-3,5-dideoxyD-glycero-β-D-galacto-2-nonulopyranosylonic acid, was tested using ITC and showed no binding interaction towards the SSS protein. So far, none of the amides have been tested due to purification issues. Models of the active site show promise for modifications at the C3 and C4 position, and these positions should be the focus of future analogues. (Less)
Popular Abstract
Sialic acid is a type of sugar present in the human body. Certain bacteria use sialic acid to hide themselves from our immune system by displaying it on their cell surface. By synthesizing sialic acid based compounds, this mechanism could be blocked generating a potential new type of antibiotics to save humanity from multi resistant bacteria.
Please use this url to cite or link to this publication:
author
Warlin, Niklas LU and Furevi, Axel LU
supervisor
organization
alternative title
Syntes av sialinsyraanaloger för undersökning av hämmande aktivitet mot bakteriella sialinsyratransportörer
course
KOK820 20161
year
type
H2 - Master's Degree (Two Years)
subject
keywords
multiresistant bacteria, Sialic acid, sialic acid derivatives, organisk kemi, antibiotics, organic chemistry
language
English
id
8893401
date added to LUP
2016-12-22 09:43:06
date last changed
2016-12-22 09:43:06
@misc{8893401,
  abstract     = {Sialic acids are monosaccharides commonly located towards the end of the glycans in the human cell membrane. Therefore, sialic acids are in direct contact with the surroundings of the cell and are important antigens involved in the identification of human cells for the immune system. Some pathogenic bacteria have developed mechanisms for absorbing this sugar, and can use it to glycosylate their lipopolysaccharides, masking them from the human immune system. As this mechanism is essential for the survival of the bacteria in the human host, preventing it may result in a new mechanism of action for antibiotics. 
By synthesizing sialic acid analogues and later testing their affinity for the sialic acid membrane protein - a sodium solute symporter (SSS) protein, new sialic acid derivatives with stronger affinity towards the active site could be constructed. We have been focusing on the synthesis of thiosialic acid derivatives of α and β stereoisomers for the sialic acid Neu5Ac, as well as different amides in the C5 position. A synthetic pathway for modifications at position C3 is also suggested. 
The affinity for the smallest of the β-thiosialic acid, 2-thioethyl-5-acetamido-3,5-dideoxyD-glycero-β-D-galacto-2-nonulopyranosylonic acid, was tested using ITC and showed no binding interaction towards the SSS protein. So far, none of the amides have been tested due to purification issues. Models of the active site show promise for modifications at the C3 and C4 position, and these positions should be the focus of future analogues.},
  author       = {Warlin, Niklas and Furevi, Axel},
  keyword      = {multiresistant bacteria,Sialic acid,sialic acid derivatives,organisk kemi,antibiotics,organic chemistry},
  language     = {eng},
  note         = {Student Paper},
  title        = {Synthesis of sialic acid analoges for investigation of antagonistic activity against bacterial sialic acid transporters},
  year         = {2016},
}