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BGM3039 - L3 Exam Study Guide
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BGM3039 - L3 Exam Study Guidewhat are some problems with therapeutic proteins - Answer -low activity
-rapid clearance
-immunogenicity
which therapeutic proteins make up more than 1/2 of the market - Answer glycoproteins
what does the biological activity of proteins depend on - Answer amino acid sequence
what do the pharmacological properties of proteins depend on - Answer carbohydrates
what pharmacological properties do carbohydrates determine - Answer stability
solubility
bioavailability
in vivo activity
pharmacokinetics
immunogenicity
what is glycosylation - Answer process of adding oligosaccharides to protein during
synthesis and processing through ER and golgi
when are glycans added - Answer post-translationally
how many human proteins are glycosylated and at how many sites - Answer half
1/more
what can effect qualitative and quantitative aspects of glycosylation - Answer
production process
what are the 2 main glycosylation linkages - Answer N and O
what do glycoproteins occur as - Answer heterogenous populations of glycoforms
what is the amino acid linked in N-linked glycosylation - Answer asparagine
where does the N-glycosidic bond form - Answer Asn-X-Ser/Thr sequence
-X any amino acid but proline/aspartic acid
which is the most prevalent and widely studied glycosylation - Answer N-linked
, what are the 3 types of N-glycans - Answer -high mannose type = yeast
-hybrid type = plant/insect
-complex type = mammalian
what do all 3 types of N-glycans have in common - Answer common polysaccharide core
(precursor)
=Man(a1,6)-Man(a1,3)-Man(B1-4)-GlcNAc(B1-4)-GlcNAc(B1-N)-Asn
what is the precursor of N-glycans - Answer dolichol
= glycolipid with pyrophosphate bond
what are the stages of N-glycan assembly - Answer 1. ribosome form polypeptide on ER
membrane
2. dolichol phosphate attach 2 phosphate in membrane
3. pick up core polysaccharide
4. translocate to lumen and add more mannose
5. secreted to golgi with glycohydrolase and glycotransferase
6. modified by adding sialic acid
which are the 3 places oligosaccharides can bind in O-glycans - Answer attached to
hydroxyl group of
-serine/threonine
-hydroxylysine (Hyl)
-hydroxyproline (Hyp)
which are the 2 types of attachment only present in collagens - Answer Hyl and Hyp
what is the first sugar residue in serine/threonine - Answer normally
N-acetylgalactosamine (GalNAc)
how long are O-glycans - Answer short = 1-20 sugar residues
what are the most common O-glycans - Answer O-linked mucin-type glycoforms
what are O-linked mucin-type glycoforms classified by - Answer 1 of 8 core structures
what is the diversity of the core O-glycan dependent on - Answer subsequent sugar
metabolism
when are O-glycans added - Answer post-translationally to exposed Ser/Thr residues of
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