Editing Glycosidic bond (section)

== O-linked glycopeptides; pharmaceutical uses of O-glycosylated peptides ==

[[File:Control of Oxonium ion - Felkin-Ahn stereoselectivity2.png|thumb|Control of oxonium ion – Felkin-Ahn stereoselectivity chair forms]]
O-linked glycopeptides recently have been shown to exhibit excellent CNS permeability and efficacy in multiple animal models with disease states. In addition one of the most intriguing aspects thereof is the capability of O-glycosylation to extend half life, decrease clearance, and improve PK/PD thereof the active peptide beyond increasing CNS penetration. The innate utilization of sugars as solubilizing moieties in Phase II and III metabolism (glucuronic acids) has remarkably allowed an evolutionary advantage in that mammalian enzymes are not directly evolved to degrade O glycosylated products on larger moieties.

The peculiar nature of O-linked glycopeptides is that there are numerous examples which are CNS penetrant. The fundamental basis of this effect is thought to involve "membrane hopping" or "hop diffusion". The non-brownian motion driven "hop diffusion" process is thought to occur due to discontinuity of the plasma membrane. "Hop diffusion" notably combines free diffusion and intercomparmental transitions. Recent examples notably include high permeability of met-enkephalin analogs amongst other peptides. The full mOR agonist pentapeptide DAMGO is also CNS penetrant upon introduction of glycosylation.<ref>{{cite journal | vauthors = Egleton RD, Mitchell SA, Huber JD, Janders J, Stropova D, Polt R, Yamamura HI, Hruby VJ, Davis TP | display-authors = 6 | title = Improved bioavailability to the brain of glycosylated Met-enkephalin analogs | journal = Brain Research | volume = 881 | issue = 1 | pages = 37–46 | date = October 2000 | pmid = 11033091 | doi = 10.1016/S0006-8993(00)02794-3 | s2cid = 18102579 }}</ref><ref>{{cite journal | vauthors = Polt R, Dhanasekaran M, Keyari CM | title = Glycosylated neuropeptides: a new vista for neuropsychopharmacology? | journal = Medicinal Research Reviews | volume = 25 | issue = 5 | pages = 557–585 | date = September 2005 | pmid = 16075406 | doi = 10.1002/med.20039 | s2cid = 38798797 }}</ref><ref>{{Cite journal|last1=Egleton|first1=Richard D.|last2=Bilsky|first2=Edward J.|last3=Tollin|first3=Gordon|last4=Dhanasekaran|first4=Muthu|last5=Lowery|first5=John|last6=Alves|first6=Isabel|last7=Davis|first7=Peg|last8=Porreca|first8=Frank|last9=Yamamura|first9=Henry I.|date=2005-01-10|title=Biousian glycopeptides penetrate the blood–brain barrier|journal=Tetrahedron: Asymmetry|series=Carbohydrate Science. Part 1|volume=16|issue=1|pages=65–75|doi=10.1016/j.tetasy.2004.11.038}}</ref>