The chemical exploration of C-C bond forming reactions on 7-position aldehyde sialic acid derivatives for bacterial transport inhibition
(2021) KASM05 20202Centre for Analysis and Synthesis
- Abstract
- The discovery of penicillin and the many antibiotics after that, has given our society a heightened sense of confidence when dealing with everything from the everyday bacterial infection to complicated surgical procedures. However, more and more bacterial species are becoming resistant to antibiotics. 33000 deaths attributed to antibiotic-resistant bacteria occurred in Europe in 2015, a number that is likely higher today and will continue to rise, creating a need for a new class of antibiotics.
The human body contains a plethora of different kinds of sugars serving various functions. One group of these sugars is called sialic acids and it is usually located at the terminal positions of glycan chains on the surface of cells. One variant... (More) - The discovery of penicillin and the many antibiotics after that, has given our society a heightened sense of confidence when dealing with everything from the everyday bacterial infection to complicated surgical procedures. However, more and more bacterial species are becoming resistant to antibiotics. 33000 deaths attributed to antibiotic-resistant bacteria occurred in Europe in 2015, a number that is likely higher today and will continue to rise, creating a need for a new class of antibiotics.
The human body contains a plethora of different kinds of sugars serving various functions. One group of these sugars is called sialic acids and it is usually located at the terminal positions of glycan chains on the surface of cells. One variant of sialic acid, called Neu5Ac, participates in many biological functions such as cell signalling, cellular adhesion, immunological response, neuroplasticity, and many others still under investigation. Despite its many vital functions, it can also be turned against its host as it has been discovered that pathogens use Neu5Ac as a carbon and nitrogen source and to avoid immunological detection. Some of these pathogens are, Escherichia.coli, Neisseria gonorrhoeae, Haemophilus influenzae, and Streptococcus agalactiae, and many others. Some bacteria can biosynthezise Neu5Ac but most resort to scavenging them of the host. Some have even developed a way to evade the immune system by putting the scavenged Neu5Ac at the surface of their cells, in a phenomenon called molecular mimicry. By modifying Neu5Ac it might be possible to inhibit the active transport and subsequent catabolism of Neu5Ac by bacteria, hindering their growth. Thus, creating a new class of antibiotics. Although many Neu5Ac derivatives have been synthesized and tested, there is still many reactions that can be investigated. This project shines a light on previously unexplored synthetic pathways using versatile name reactions. (Less) - Popular Abstract
- Chemistry is one of the oldest scientific disciplines in the world. Whether it is in the ironworks of medieval Europe, the alchemy in the caliphs court in Baghdad, or the herbal teas of in the times of the various Chinese dynasties. Humans have historically tried to alter or manipulate their environment to overcome challenges and survive. Many great chemical inventions have helped to create the world we live in today. When new challenges arise humans innovate and create new solutions. One of our historical foes is bacteria and the fight with it has been long and difficult. The discovery of antibiotics brought us the ability to survive infections that would have been deadly prior to its discovery. It helped prolong our lives by enabling us... (More)
- Chemistry is one of the oldest scientific disciplines in the world. Whether it is in the ironworks of medieval Europe, the alchemy in the caliphs court in Baghdad, or the herbal teas of in the times of the various Chinese dynasties. Humans have historically tried to alter or manipulate their environment to overcome challenges and survive. Many great chemical inventions have helped to create the world we live in today. When new challenges arise humans innovate and create new solutions. One of our historical foes is bacteria and the fight with it has been long and difficult. The discovery of antibiotics brought us the ability to survive infections that would have been deadly prior to its discovery. It helped prolong our lives by enabling us to perform complicated surgeries and it made our food safer to consume.
However, bacteria evolve, and our dependence on antibiotics has created antibiotics resistant bacteria which is a growing problem in the world we live in today. Imagine if a simple infection could result in death? This scenario is already a reality to a small extent but will become more and more common in the future. How we combat this issue exactly is not certain but one of the answers might lay in one of our most common molecules, carbohydrates. Carbohydrates serve many different functions in the body. One of these carbohydrate families that is present on the surfaces of cells are sialic acids. Sialic acids take part in many functions such as cell signalling, neuroplasticity, and the regulation of the immune response. Sialic acids, however, also serves as a carbon and nitrogen source for intruding pathogens. These pathogens transport sialic acids into their cells and catabolize it. Some can also use it as a disguise to hide from our immune cells.
Various institutions around the world have made efforts to modify the most common sialic acid in humans, N-Acetylneuraminic acid or Neu5Ac, but the research in Lund University is the only one targeting the bacterial transport proteins. Blocking the bacterial transport of Neu5Ac could possibly inhibit the growth and spread of these intrusive pathogens and lead to the discovery of a new class of antibiotics, which would save many lives.
In this project we added to the research of sialic acid by discovering new synthetic paths to modify the 7th position carbon on Neu5Ac. Reactions such as Sonogashira, Horner-Woodsworth-Emmonds, and 1,3-Dipolar cycloadditions proved to be possible and produced compounds that are going to be tested against 4 different target proteins that are necessary for the transport of Neu5Ac. These reactions also opened new possibilities for further modifications, increasing the library of possible reactions on Neu5Ac. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9041260
- author
- Azawee, Elias LU
- supervisor
-
- Ulf Nilsson LU
- organization
- course
- KASM05 20202
- year
- 2021
- type
- M1 - University Diploma
- subject
- keywords
- pharmaceutical technology, Medicinal chemistry, inhibitors
- language
- English
- id
- 9041260
- date added to LUP
- 2021-03-18 16:18:32
- date last changed
- 2021-03-18 16:18:32
@misc{9041260,
abstract = {{The discovery of penicillin and the many antibiotics after that, has given our society a heightened sense of confidence when dealing with everything from the everyday bacterial infection to complicated surgical procedures. However, more and more bacterial species are becoming resistant to antibiotics. 33000 deaths attributed to antibiotic-resistant bacteria occurred in Europe in 2015, a number that is likely higher today and will continue to rise, creating a need for a new class of antibiotics.
The human body contains a plethora of different kinds of sugars serving various functions. One group of these sugars is called sialic acids and it is usually located at the terminal positions of glycan chains on the surface of cells. One variant of sialic acid, called Neu5Ac, participates in many biological functions such as cell signalling, cellular adhesion, immunological response, neuroplasticity, and many others still under investigation. Despite its many vital functions, it can also be turned against its host as it has been discovered that pathogens use Neu5Ac as a carbon and nitrogen source and to avoid immunological detection. Some of these pathogens are, Escherichia.coli, Neisseria gonorrhoeae, Haemophilus influenzae, and Streptococcus agalactiae, and many others. Some bacteria can biosynthezise Neu5Ac but most resort to scavenging them of the host. Some have even developed a way to evade the immune system by putting the scavenged Neu5Ac at the surface of their cells, in a phenomenon called molecular mimicry. By modifying Neu5Ac it might be possible to inhibit the active transport and subsequent catabolism of Neu5Ac by bacteria, hindering their growth. Thus, creating a new class of antibiotics. Although many Neu5Ac derivatives have been synthesized and tested, there is still many reactions that can be investigated. This project shines a light on previously unexplored synthetic pathways using versatile name reactions.}},
author = {{Azawee, Elias}},
language = {{eng}},
note = {{Student Paper}},
title = {{The chemical exploration of C-C bond forming reactions on 7-position aldehyde sialic acid derivatives for bacterial transport inhibition}},
year = {{2021}},
}