Glycoconjugates

proteoglycans

macromolecules in ECM

Extracellular matrix components

proteoglycan aggregates, collagen fibers, elastin

Aggrecan

a type of proteoglycan in cartilage ECM, covalent and non-covalent aggregates of protein and glycosaminoglycans

glycosaminoglycans

linear polysaccharide chains of repeated disaccharide units

typical residues:

• uronic acid

• galactose

• N-acetylglucosamine

• N-acetylgalactosamine

collagen

fibrils complexed with proteoglycans; proteoglycan-hyaluronate aggregates are highly saturated with water; helps with flexibility and shock absorbance

Peptidoglycan

a component of bacteria cell walls; 3D mesh like layer that protects cell from osmotic pressure; beta(1→4) linked N-acetylmuramic acid and N-acetylglucosamine; peptide component is D-amino acids containing tetrapeptides

Gram positive bacteria

Thicker layer of peptidoglycan, pentaglycine bridge connects tetrapeptides

Gram negative bacteria

thin layer of peptidoglycan, direct crosslinking of tetrapeptides

lysozyme

antimicrobial enzyme that breaks nown cell walls, peptidoglycan is resistant to proteases by not lysozymes: cleaves beta(1→4) linkage between NAM and NAG

Glycoproteins

proteins with covalently linked oligo- or polysaccharide groups; carbohydrate group attached via anomeric carbon

O-glycosylation

glycosidic bond to hydroxyl group of threonine or serine

N-glycosylation

glycosidic bond to amide nitrogen of asparagine residue

Functions of glycosylation

increases complexity of proteome, affect physical and chemical properties of proteins, contributes to correct folding (N-glycosylation), targeting of glycoproteins to particular cellular locations, specific functions at cell surface

Lectins

molecules that recognize carbohydrate structures recognized with high specificity; important in cell-cell recognition signaling and adhesion

Hemagglutinin

a glycoprotein expressed on the surface of the influenza virus, binds to sialic acid on oligosaccharides of cell surface glycoproteins or glycolipids to facilitate entry to the cell; bifunctional (recognition and fusion)

Neuraminidase

viral-surface protein, enzyme cleaves oligosaccharide chains to release the viral particle at later stages of viral life cycle

Heparin

anticoagulant, repeated glycosaminoglycan in linear chain; binds cationic site of anti-thrombin III to induce conformational change that promotes inhibitory action

carbohydrates in therapeutics

heparin, synthetic glycopeptides, homogenous therapeutic antibodies, antibody drug conjugates, antibacterial vaccine, glycoconjugate anti-HIV vaccine, glycogonjugate anti-cancer vaccine, GalNAc oligonucleotide conjugate, in-vivo glycoengineering