Synthesis of sialic acid 4-C derivatives through alkyne nucleophilic addition with the ambition to develop efficient inhibitors of bacterial transport proteins
(2021) KEMR30 20202Department of Chemistry
- Abstract
- Antimicrobial resistance is according to the World Health Organization (WHO) one of the most rapidly growing threats to world health. According to a recently published WHOreport, drug resistant microbials could be responsible for up to 10 million annual deaths by the year 2050 unless drastic measures are taken such as decreasing misuse and developing new antibiotics. This work explores the possibility of using modified structures of the sugar
named Neu5Ac, more commonly referred to as just sialic acid, in hopes of creating a new type of antibiotic.
Sialic acids are commonly found on the outside of human cells. Besides being used as an energy and atom source, a large range of pathogenic bacteria such as P.mirabilis and S.aureus utilize... (More) - Antimicrobial resistance is according to the World Health Organization (WHO) one of the most rapidly growing threats to world health. According to a recently published WHOreport, drug resistant microbials could be responsible for up to 10 million annual deaths by the year 2050 unless drastic measures are taken such as decreasing misuse and developing new antibiotics. This work explores the possibility of using modified structures of the sugar
named Neu5Ac, more commonly referred to as just sialic acid, in hopes of creating a new type of antibiotic.
Sialic acids are commonly found on the outside of human cells. Besides being used as an energy and atom source, a large range of pathogenic bacteria such as P.mirabilis and S.aureus utilize sialic acids to evade the host’s immune system.
This is achieved through something that is called molecular mimicry. By obtaining these sugars from glycoconjugates on human cells, they can transport them into their own cells through specific transporter-proteins and reattach them onto their own surface. This masks them from the immune system of the host and allows the bacteria to proliferate.
In a recent article from 2018 published In Nature communications, Wahlgren et al.characterized one of these sialic acid transporters, a sodium solute symporter (SSS) protein named Sialic Acid Transporter (SiaT). This gave a massive insight into the geometry of the active site. In light of this newfound knowledge, members of the Ulf Nilsson group have set out to modify sialic acid to increase the affinity for SiaT with the ambition of creating potent inhibitors.
This work specifically focuses on modifying the 4-C position of sialic acid with the approach of forming new C-C bonds instead of previously made C-O-C bonds in hopes of creating high affinity compounds and increasing the SAR knowledge of the region.
Although new C-C bonds were created selectively using a rather unusual approach of cerium chemistry, the target compounds have within the timeframe of this project not been reached. It is however likely that the obstacles that remain to overcome could be solved
soon. (Less) - Popular Abstract
- Antimicrobial resistance is according to the World Health Organization (WHO) one of the most rapidly growing threats to world health. According to a recently published WHO report, drug resistant microbials could be responsible for up to 10 million annual deaths by the year 2050 unless drastic measures are taken such as decreasing misuse and developing new antibiotics.
This work explores the possibility of changing the structure of a sugar named sialic acid, in hopes of creating a new type of antibiotic.
Sialic acids are commonly found on the outside of human cells. Besides being used as an energy and atom source, a large range of harmful bacteria utilize sialic acids to evade the host’s immune system.
This is achieved through... (More) - Antimicrobial resistance is according to the World Health Organization (WHO) one of the most rapidly growing threats to world health. According to a recently published WHO report, drug resistant microbials could be responsible for up to 10 million annual deaths by the year 2050 unless drastic measures are taken such as decreasing misuse and developing new antibiotics.
This work explores the possibility of changing the structure of a sugar named sialic acid, in hopes of creating a new type of antibiotic.
Sialic acids are commonly found on the outside of human cells. Besides being used as an energy and atom source, a large range of harmful bacteria utilize sialic acids to evade the host’s immune system.
This is achieved through something that is called molecular mimicry. By obtaining these sugars from the surface of human cells, they can transport them into their own cells through specific transporter-proteins and reattach them onto their own surface. This masks them from the immune system of the host and allows the bacteria to grow.
In this project two new molecules that mimic sialic acid and could potentially block the uptake of sialic acid were made starting from the natural sugar. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9041166
- author
- Lumetzberger, Max LU
- supervisor
-
- Ulf Nilsson LU
- organization
- course
- KEMR30 20202
- year
- 2021
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Organic chemistry, Organic synthesis, Sialic Acid, Carbohydrates
- language
- English
- id
- 9041166
- date added to LUP
- 2021-03-02 15:21:05
- date last changed
- 2021-03-02 15:21:05
@misc{9041166,
abstract = {{Antimicrobial resistance is according to the World Health Organization (WHO) one of the most rapidly growing threats to world health. According to a recently published WHOreport, drug resistant microbials could be responsible for up to 10 million annual deaths by the year 2050 unless drastic measures are taken such as decreasing misuse and developing new antibiotics. This work explores the possibility of using modified structures of the sugar
named Neu5Ac, more commonly referred to as just sialic acid, in hopes of creating a new type of antibiotic.
Sialic acids are commonly found on the outside of human cells. Besides being used as an energy and atom source, a large range of pathogenic bacteria such as P.mirabilis and S.aureus utilize sialic acids to evade the host’s immune system.
This is achieved through something that is called molecular mimicry. By obtaining these sugars from glycoconjugates on human cells, they can transport them into their own cells through specific transporter-proteins and reattach them onto their own surface. This masks them from the immune system of the host and allows the bacteria to proliferate.
In a recent article from 2018 published In Nature communications, Wahlgren et al.characterized one of these sialic acid transporters, a sodium solute symporter (SSS) protein named Sialic Acid Transporter (SiaT). This gave a massive insight into the geometry of the active site. In light of this newfound knowledge, members of the Ulf Nilsson group have set out to modify sialic acid to increase the affinity for SiaT with the ambition of creating potent inhibitors.
This work specifically focuses on modifying the 4-C position of sialic acid with the approach of forming new C-C bonds instead of previously made C-O-C bonds in hopes of creating high affinity compounds and increasing the SAR knowledge of the region.
Although new C-C bonds were created selectively using a rather unusual approach of cerium chemistry, the target compounds have within the timeframe of this project not been reached. It is however likely that the obstacles that remain to overcome could be solved
soon.}},
author = {{Lumetzberger, Max}},
language = {{eng}},
note = {{Student Paper}},
title = {{Synthesis of sialic acid 4-C derivatives through alkyne nucleophilic addition with the ambition to develop efficient inhibitors of bacterial transport proteins}},
year = {{2021}},
}