glycoconjugates

glycoconjugates

1. all life is covered by glucans

   • Glucobiology is an integral and fascinanting aspect of cell biology and medical implications
   • conoaflagelates
     • mating behavior
   • legumes
     • beneficial interactions between root and soil bacterias

2. glycans

   • consisting of monosaccharides or individual sugars which aren´t hydrolysed to simple forms
   • stereochemistry is important
     • two glucans with chemical forms and connectivity of equal but stereochemically distinct atoms
       • different biological properties
         • glucose vs. cellulose
   • a lot of structural variability
     • increases with branching

3. eukaryotes

   • most glycoproteins and glycolipids are synthesized in the endoplasmic reticulum and in Golgi
   • glycosylation is abundant in animal and plant cells
     • variability makes it more difficult for viruses and parasites to explore
   • microheterogeneity
     • a protein can exist in multiple glycogens within the same cell or tissue
   • macroheterogeneneity
     • a single specific protein can be glycosylated differently in one tissue versus another

4. functions

   • structural integrity to cells and tissues
   • passive signalling
   • in the ER to secrete only well-folded substances
   • regulation of endocytosis and protein trafficking
   • membrane organization and signalling and nutrient storage
   • diseases with aberrant glycosylations
     • cancer
     • neurodegeneration
     • diabetes
     • treatments with glycoconjugates
       • heparine
       • aminoglycosidic antibiotics
       • erythropoietin
       • vaccines

5. manu cell surface proteins need specific glucans to perform their work

   • NOTCH
     • Important glycosylation during the embryogenesis of vertebrates
       • reinforces bond between the receptor and the ligand
     • cancer therapies
   • high and dense glucocaylic comes fron the activation of integrines
     • can promote the survival and proliferation of tumor cells,
       • usually have abnormalities in glucocylic
   • as the cover surfaces
     • are first-line mediators between species
       • human intestinal microbiome
         • can improve health by rational manipulation of gut microbiome using probiotin glucans
     • mice
       • damage in a gen modifies his microbiome
     • relationship between dietary carbohydrates and intestinal flora

6. O-GlcNAc

   • nutrient detection
   • metabolically importanpathways and processes
     • cardiac calcium signaling
     • mitochondrial motility in neurones
   • stress signaling redox
   • protein traffic
   • is added to substrates metabolically by OGT glicotransferase

7. molecular and chemical part

   • Synthesis
     • VIH-1 antibodies can be obtained throught the synthesis of glucopeptides
     • potential vaccines against cancer, viruses and bacterias
     • biotechnological tool
     • necessary chemoselectivity and stereoselectivity for the formation of specific glycosides
       • many possibilities
     • two ways
       • early formation of glycan-aglycone bond by assembly of protected or partiallu protected glycosylated building blocks
       • blocks are built independently, the link is created later in the synthesis
   • various carbohydrates unificated covalently to no-sugars as proteins, peptides and lipids
   • parts of sugar are important in cell recognition and biological activity control.
   • glycopeptides and glycoproteins
     • glycosidic bond formation necessary to covalently connect a sugar molecule to anothe group that can not be a sugar
     • have been prepared from glycans
       • by linear assembly of glycosylated amino acids
         • less tan 50 amino acids
       • converging condensation of peptide/glucopetide builidng blocks not protected or partially protected
         • acid base lability of glycosidic bond
       • direct coupling between a glucosamine and an aspartic acid peptide
         • advantage: manipulations to the minimum
         • problem in efficiency and there are undesirable links
       • chemotherapeutic ligation as an alternative
         • disadvantage in the inherent instability of peptide thiosters
           • hard synthesis and manipulation
           • glycotransferases have been studied for the process
             • low efficiency
             • the are glycosidic links the can't access
     • glycoproteins
       • natural as are complex mixtures of glycogens
         • same protein skeleton but differ in oligosaccharide components and glycosylation sites
           • as the behave differentlu, their synthesis is a challenge
             • synthetics are limited in size
       • syntheis of the extracellular IG domain of EMMPRIN
         • glycoprotein that is enriched on the surface of tumor cells
   • glicolipids
     • usefull in pharmaceutical formulations
     • sugars covalently bound to lipids
     • amphipatics
       • ability to self-insert into cell membranes
     • behavior similar to that of the othe glucoconjugates
     • were classified based on their lipid remains
       • glucoglicerolipids
       • glucofosfatidilinositols
       • glucoesfingolipids
         • from bacterias to humans
         • each has a specific biological fuction
         • effort in the synthesis of analogues
           • difficulty to control stereochemistry of the glycosidic bond
           • glucosil iodide chemistry has been used in its synthesis successfully
           • with microwaves the reaction time is improved when using saturated ceramides
             • ceramides
               • low nucleophilia
             • waves alter the packaging of lipids making the acceptor more accesible
               • increase in the number of reactions
     • antibodies in the late stage of Lyme disease

8. the synthesis is delayed by the processes of protection, efficiency is reduced

   • carbohydrates are cheap, but derivatization isn't
     • carbohydrate bioengineering as an option to make processes impler, more efficent and faster