Related Experiment Video
Updated: Mar 6, 2026
12:06
Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
Published on: November 25, 2017
13.5K
Conformational Behaviour of Azasugars Based on Mannuronic Acid
Erwin R van Rijssel1, Antonius P A Janssen1, Alexandra Males2
1Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Chembiochem : a European Journal of Chemical Biology
|March 4, 2017
Summary
Mannuronic-acid-based iminosugars were synthesized and their pH-dependent shapes studied. These compounds showed pH-driven conformational changes, impacting their potential as enzyme inhibitors.
Area of Science:
- Carbohydrate Chemistry
- Enzyme Inhibition
- Structural Biology
Background:
- Iminosugars are carbohydrate mimics with therapeutic potential.
- Mannuronic acid derivatives offer unique structural properties.
- Understanding conformational dynamics is key to enzyme inhibition.
Purpose of the Study:
- To synthesize mannuronic-acid-based iminosugars.
- To investigate their pH-dependent conformational behavior.
- To evaluate their potential as inhibitors for glycosidases.
Main Methods:
- Chemical synthesis of iminosugar analogues.
- Nuclear Magnetic Resonance (NMR) spectroscopy for conformational analysis.
- X-ray crystallography for structure determination of enzyme-inhibitor complexes.
Main Results:
- Synthesized mannuronic acid iminosugars exhibited pH-dependent conformational changes.
- The methyl ester and carboxylic acid analogues adopted an "inverted" 1C4 conformation at acidic pH.
- No binding was observed for the mannuronic acid ester azasugar with Caulobacter GH47 mannosidase.
- 1-Deoxymannojirimicin (DMJ) bound to CkGH47 in two conformations (3S1 and 1C4).
Conclusions:
- The synthesized iminosugars display pH-sensitive conformational flexibility.
- This flexibility influences their interaction with glycosidases.
- Further studies are needed to optimize iminosugar inhibitors based on these findings.
Related Concept Videos
01:24Oligosaccharide Assembly
3.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
3.8K
01:25Protein Glycosylation
10.1K
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
10.1K
01:05Proteoglycans
5.0K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
5.0K
03:25Chemistry of Carbohydrates
92.3K
Carbohydrates are an essential part of the diet in humans and animals. Grains, fruits, and vegetables are natural sources of carbohydrates that provide energy to the body, particularly through glucose, a simple sugar that is a component of starch and an ingredient in many staple foods. The stoichiometric formula (CH2O)n, where n is the number of carbons in the molecule represents carbohydrates. In other words, the ratio of carbon to hydrogen to oxygen is 1:2:1 in carbohydrate molecules. This...
92.3K
03:25Chemistry of Carbohydrates
11.0K
11.0K
01:23Glycosaminoglycans
7.4K
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
7.4K