???????? Glycobiology and Glycomics ????????? ?????? ??

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????????Glycobiology and Glycomics????????????
?????
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• ?????
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• 1,????
• 2,????????
• 3,???????????
• 4,?????????
• 5,?????????
• 6,??????????????
• 7,???????

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• 1, ????
• ???? Glycosciences
• Glycochemistry
• Glycobiology
• Glycotechnology glycoengineering
• ????????
• Glycoimmunology
• Carbohydrate histochemistry
• Sialobiology (??????)
• ?????? (Chemical Glycobiology)

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?? ???????

• 1, ????
• ???? Glycosciences
• Glycobiology Study of the structure,
  chemistry, biosynthesis, and biological functions
  of glycans and their derivatives.
• ????(Glycobiology)?????(??????)??????????????????
  ???????????,??????????????????????????????

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• Glycobiology
• ?????????????????????????????????????,????????????
  ?????????????.
• ????????????????????????????????????????????????.

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• Glycobiology
• ?????????????????????.
• 6??????????????105??????,
• ?6??????????1012??????

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• 1, ????
• ????????
• ??????????????????????,?????????????
• (1)?????????????
• Landsteiner 1930????????????????????????????????
  ??????????????????????????????

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?? ???????

• ????????
• (2)???????
• ???????????????,?????????????,?????????????????,??
  ??????????????????????????????????????????????????
  ,???????????,???????????(????)??????(?????)???????

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?? ???????

• ????????
• (2)???????
• ????????????????????????????????,?????????????????
  ??????????????????????????????????????????(tunicam
  ycin)???????(deoxynojirimycin)?????(swainsonine)??
  ??????????,?????????????????

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?? ???????

• ?? ?????????????????????????
• (1)??????????????????
• ????????????????
• ????H2S???????????????
• ??????????????????

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?? ???????

• ?? ?????????????????????????
• (2)??????????
• ????????????????????????
• (3)??????????
• ?????

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?? ???????

• 1, ????
• ????????
• E. Fischer ????????? ?????????????????,
  ?1902??????
• ??????????????????????????????????? (Gest
  Schopf) ?
• 50??????????????
• 80?????????????,????
• 90??glycogene KO mouse (glycogene knock out)
• 2003 Glycomics

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?? ???????

• Genome
• ?
• Transcriptome
• ?
• Proteome
• ?
• Glycome

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• 1, ????
• ??(Glycome)??????????????????????,?????????(????
  ???)?????,??????????????????????
• ???(Glycomics)??????????????????????????????,???
  ??????????????????????????????

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• ??(Glycome)By analogy to the genome,
  transcriptome, or proteome, the glycome is
  the complete set of glycans and glycoconjugates
  that are made by a cell or organism under
  specific conditions. Therefore, glycomics
  refers to studies that attempt to define or
  quantify the glycome of a cell, tissue, or
  organism.-----Glycomics Hits the Big Time Gerald
  W. Hart and Ronald J. Copeland. Cell 143,
  November 24, 2010, 673

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?? ???????

• 2, ????? (Bioconjugates) ???
• ????????????????????????????????(modules,
  buiding blocks),??????????????????????????,??????(
  bioconjugates)?
• ???????????
• ?????????????,???????,???????????,???????????????
  ?????????????
• ????The Bioconjugate Journal

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?? ???????

• 2, ????? (Bioconjugates) ???
• ???????????????????????????,???????????,??????????
  ????????,?
• ????/???????????????
• ???????????????????(Glycoconjugates, ????)?

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?? ???????

• ???????????
• ????
• ?????
• ????
• ??????????

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2, ????? (Bioconjugates) ???

• ????????????
• ??????????????????
• ??????????(???,aglycone)????????????????(glycoconj
  ugates,????????????)?
• ??????????
• ???????,??????????,??????????????85????????????
• ??????

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?? ???????

• ???????????????????????????????????,??????????
  ????????????????????,?????????????????????,???????
  ??????????,?????????????????2000??25???
• ?????Nature?Science?Cell?????????????????????,????
  ??????????????????????????????????????

22
?? ???????

• ???????,?????????????,???(Glycomics)??????????
  ???????,???????????????????????(??NIH????)????????
  ??????????Griffith??,??2000?????????,?????Mark
  von Itzstein????????Zanamivir(???Relenza),????????
  ?????????????????,????????????????????????????????
  ?????????????????????????????,????????????????????
  ???????????

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• ???MIT?????????30?????????????????????????????
  ?????Technology Review,?2003?1?21???????,?????????
  ???????????????2003?GlycoSuiteDB(5.0?)??????,?????
  ??187????????8100??????,???890?N-??????709?O-?????
  ???85???????????????????

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• 7.1, ??????????
• Gest? Schopf???????????????????????????????????
  ?
• Scientists are saying that glycomics could fuel a
  revolution in biology to rival that of the human
  genome. New Scientist, Oct. 2002
• Sharon, N. ????????????????????????

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• ??????????????????????????????????
• ????
• ????? ?
• ????????????????
• ???????
• ??????????????

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• ????????????
• ????????1000?????????????????????????????????100
  0??
• ??????????300??

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• ??????????????????
• ???????????????
• ???????????????????????????????????????

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• 3, ???????????
• 3.1, ?????
• ?,?????,?(?,???)
• 3.1.1, Carbohydrate A generic term used
  interchangeably with sugar, saccharide, or
  glycan. It includes monosaccharides,
  oligosaccharides, and polysaccharides as well as
  derivatives of these compounds.

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?? ???????

• 3.1.2, Saccharide(??)
• Monosaccharides(??)
• Carbohydrate that cannot be hydrolyzed into a
  simpler carbohydrate. The building block of
  oligosaccharides and polysaccharides. Simple
  monosaccharides are polyhydroxyaldehydes or
  polyhydroxyketones with three or more carbon
  atoms.
• Oligosaccharides(??)
• Polysaccharides(??)

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• 3.1.3, Sugar A generic term often used to refer
  to any carbohydrate, but most frequently to
  low-molecular-weight carbohydrates that are sweet
  in taste. Table sugar, sucrose (Fruß2-1?Glc), is
  a non-reducing disaccharide. Oligosaccharides are
  sometimes called "sugar chains" and individual
  monosacchandes in a sugar chain are sometimes
  referred to as "sugar residues".
• ?????,?????

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?? ???????

• 3.1.4, Glycoside(??) A glycan containing at
  least one glycosidic linkage to another glycan or
  an aglycone(??).
• 3.1.5, Glycan A generic term for any sugar or
  assembly of sugars, in free form or attached to
  another molecule, used interchangeably with
  saccharide or carbohydrate.
• Glycan???????????????????

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?? ???????

• 3.2, ????????
• ?????? (polyhydroxyaldehydes or
  polyhydroxyketones)
• ?????????(??????)
• ???,????????????? facet
• ??????????
• ?????????
• ????????

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• 3.3, ?????????
• 3.3.1, ???????
• ????????

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• 3.3.2, Glycoconjugate(???? / ????)
• A molecule in which one or more glycan units
  are covalently linked to a noncarbohydrate
  entity.
• ?????????????
• DNA?RNA
• ?????????
• ??????(????????????)?

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• 3.3.3, Aglycone(??)
• Noncarbohydrate portion of a glycoconjugate or
  glycoside that is glycosidically linked to the
  glycan through the reducing terminal sugar.

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• 4,?????????
• ??????????????????????????
• ?????????????
• ???????????????
• ?????????????????
• ?????????????????

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• 4,?????????
• 4.1, Hexose(??)
• A 6-carbon monosaccharide typically with an
  aldehyde (or potential aldehyde) at the C-1
  position (aldohexose) and hydroxyl groups at all
  other positions. Common examples in vertebrate
  glycans are mannose, glucose, and galactose.

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• 4.2, Aldose(??) A monosaccharide with an
  aldehyde group or potential aldehydic carbonyl
  group (by definition, this is the C-1 position).
• 4.3, Ketose(??) A monosaccharide with a ketone
  group or a potential ketonic carbonyl group
  (typically at the C-2 position in natural
  compounds).

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• 4.4, Hemiacetal(???) A compound formed by
  reaction of an aldehyde with an alcohol group, as
  in ring closure of an aldose.
• 4.5, Acetals(??) An organic compound derived
  from a hemiacetal by reaction with an alcohol. If
  the hemiacetal is a sugar, the acetal is a
  glycoside.

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• 4.6, Hemiketal(???) A compound formed by
  reaction of a ketone with an alcohol group, as in
  ring closure of a ketose.
• 4.7, Ketal(??) An organic compound derived
  from a hemiketal by reaction with an alcohol. If
  the hemiketal is a sugar, the ketal is a
  glycoside.

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• 4.8, Furanose(???) Five-membered (four carbons
  and one oxygen, i.e., an oxygen heterocycle) ring
  form of a monosaccharide named after the
  structural similarity to the compound furan.
• 4.9, Pyranose(???) Six-membered (five carbons
  and one oxygen, i.e, an oxygen heterocycle) ring
  form of a monosaccharide the most common form
  found for hexoses(??) and pentoses(??). The name
  is based on the structural similarity to the
  compound "pyran."

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• 4.10, Amino Sugar A monosaccharide in which an
  alcoholic hydroxyl group is replaced by an amino
  group.
• 4.11, Hexosamine Hexose with an amino group in
  place of the hydroxyl group at the C-2 position.
  Common examples found in vertebrate glycans are
  the N-acetylated forms, N-acetylglucosamine and
  N-acetylgalactosamine.

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• 4.12, Isomers(?????)
• 4.13, Enantiomers(???????)
• L,D
• 4.14, Epimers(?????,????) Two isomeric
  monosaccharides differing only in the
  configuration of a single chiral carbon. For
  example, mannose is the C-2 epimer of glucose.
• Epimerase An enzyme that catalyzes
  racemization(??) of a chiral center in a sugar.

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• 4.15, Mutarotation(??????)
• ??????,????????,????5???(Species)? Glc
  ???????????????
• The five species of D-Glc are
• ??????-D-Glcf, ?-D-Glcf,
• ??????-D-Glcp, ?-D-Glcp,
• Aldo-D-Glc(??????????,???? 30oC ????????)

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• 5,?????????
• 5.1, ???????
• 5.1.1, Glycosidic linkage(???)
• Linkage of a monosaccharide to another residue
  via the anomeric hydroxyl group (???). The
  linkage generally results from the reaction of a
  hemiacetal with an alcohol (e.g., a hydroxyl
  group on another monosaccharide or amino acid) to
  form an acetal.

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• 5.1.2, Anomericity(????)
• The ? or ? configuration of the glycosidic
  bond of a sugar to another sugar or an aglycone.
• 5.1.3, Anomers Stereoisomers of a
  monosaccharide that differ only in configuration
  at the anomeric carbon(?????????) of the ring
  structure (i.e., the C-1 position in a cyclic
  hemiacetal.

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• 5.2, ?????
• 5.2.1, Reducing Terminus (Reducing End,????)
  The end of a glycan that has reducing power
  because it is unattached to an aglycone and is
  thus a hemiacetal. In a glycoconjugate, reducing
  terminus is also used as a synonym for a
  potential reducing terminus, referring to the end
  of a glycan covalently attached to the aglycone
  by a glycosidic bond (i.e., it would have
  reducing power if it were released).

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• 5.2, ?????
• 5.2.2, Nonreducing Terminus (Nonreducing
  End,?????)
• The outermost end of an oligosaccharide or
  polysaccharide chain, opposite to that of the
  reducing end.

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?? ???????

• 5.3, ??????????
• Antenna(??) A branch of an oligosaccharide
  emanating from a "core" structure.
• 5.4,????????????
• ????,????????????
• ????????????

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?? ???????

• 5.5, ???????
• 5.5.1, Glycosylation(???)
• The enzyme-catalyzed covalent attachment of a
  carbohydrate to a polypeptide, lipid,
  polynucleotide, carbohydrate, or other organic
  compound, generally catalyzed by
  glycosyltransferases, utilizing specific sugar
  nucleotide donor substrates.

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?? ???????

• 5.5.2, Glycation(??)
• The nonenzymatic(?????), chemical modification
  of proteins by addition of carbohydrate, usually
  through a Schiff-base reaction (??????)with the
  amino group of the side chain of lysine and
  subsequent Amadori rearrangement to give a stable
  conjugate. Not to be confused with (enzymatic)
  glycosylation.

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?? ???????

• 5.5.2, Glycation(??)
• Carbohydrate proteins ? nonenzymatic(?????) ?
  ?????? (Schiff-base) ? ?????Amadori rearrangement
  (Amadori??) ?????????(Advanced glycation
  end-products, AGE). AGE age RAGE AGE
  receptors
• sRAGE soluble RAGE, ???AGE?????EAGE???,???AGE???
  ??????????,??????????????

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?? ???????

• 5.5.2, Glycation(??)
• ???
• (1)?????????????
• (2)???????????????????????????????

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?? ???????

• 5.5.2, Glycation(??)
• ???
• (3)??????????????????????????
• (4)?????????,?????????????????,????????????

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?? ???????

• ??????????
• 1)????????????????????????????????(??????????/????
  ???)??
• ????????????????(common adult-onset
  diseases)???
• ???????????????
• 2)???????????
• ??????

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?? ???????

• ????????????????????
• Glycation AGE age AGEs ? NF-?B
• GlcNAc???? GlcNAc?????????????????GlcNAc????,??UD
  P-GlcNAc??? UDP-GlcNAc??????????ATP???(1-2mM),????
  ?????????? UDP-GlcNAc??????/??????O-GlcNAcylation?
  ?,????????????????GlcNAc????????????????????,?TGF-
  ???

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• ????????
• 1)?????????2000?Nishikawa?????????????????????
  ???????????????????????????????????,?????????????A
  GEs??????????,????? NF-?B?????

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• ????????
• 2)??????????????
• ???????,??????????????????????????????????????????
  ?????????????????????????,????????ApoB-AGEs???????
  ???2?, Lipid-AGEs????4??

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• ????????
• 3)AGEs?????????
• AGEs???????????????????????????
• (a)??????????????????? ???????????????????????????
  ??????????????,?????????????????????????????,?????
  ?????????????????????,????????????????????????????
  ????????????????,???????

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• ????????
• (b)?AGEs??????????????????????????????????,??????
  ????????,??IL-1?IL-6?TNF-?????????????????????????
  ???????,??????????????

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• ????????
• 4) AGEs?????
• ???????????AGEs?????????????????AGEs??,?????????AG
  Es?????????????
• ????, AGEs?????????????????????,???????????????NF-
  ?B??????,???NF-?B ?????????,??????(IL-1?IL-6?TNF-?
  )?????????????,?????????????????

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• ????????
• 5) ??????????
• AGEs??????????,???????????????????????????????????
  ??????

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• ????????
• 6) ??????????????
• ??????????
• ?????????????
• ??????AGEs??
• ???????,??AGEs??????
• ??????????????
• ??????????????????????????,??AGEs???

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• 5.6, Glycomimetics(????)
• Noncarbohydrate compounds that mimic the
  properties of saccharides.
• ????

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?? ???????

• 5.7, ????????????(Diversity and heterogeneity)
• ?????
• ?????
• ????????
• ????????????
• ?????????????

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?? ???????

• 5.7.1, Microheterogeneity(??????) Structural
  variations in the glycan at any given
  glycosylation site on a protein (one source of
  glycoforms).
• 5.7.2, Glycoforms(??) Different molecular forms
  of a glycoprotein, resulting from variable glycan
  structure and/or glycan attachment site
  occupancy.
• 5.7.3, Glycotypes Cell-type-specific
  glycoforms of a polypeptide.

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?? ???????

• ????????????????
• ??????????????
• ?????????
• ?????????????
• ?????????????
• ?????????? (????????)?

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?? ???????

• 6,??????(?????)??????????(11?)
• Hexose Gal, Man, Glc, Fuc
• Pentose Xyl
• Hexosamine GlcNAc, GalNAc, GlcN
• Sialic acid Neu5Ac
• Uronic acid GlcA, IdoA

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?? ???????

• 6,??????(?????)????11?????
• Gal Galactose ??? Man Mannose ???
• Glc Glucose,??? Fuc Fucose ???
• Xyl Xylose,??
• GlcNAcN-???????, GlcN?????,
• GalNAcN-???????
• Sialic acid,??? Neu5AcN-??????
• Uronic acid,??? GlcA?????,
• IdoA?????

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• ?????????????????
• Free Glc exist predominantly in ring forms.
• Finding Glc residues in a glycoconjugate sample
  means
• Free metabolic Glc not totally removed
• Bacteria contamination
• Glycolipids premature ER-proteins
• Rare glycans in glycoproteins O-Glc (in factors
  VII, IX) Glc-Asn (laminin), etc.

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7,???????

• ???????? http//www.glycobiology.org
• Glycobiology????www.glycob.oupjournals.org
• NIH????????????(The Consortium for Functional
  Glycomics, CFG)www.functionalglycomics.org
  (??????????????)

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7,???????

• ????? http//www.glycoforum.gr.jp
• http//www.glycosuite.com ( glycosuiteDB?????)
• http//www.glycogenomics.org/?????????????????
• ??????????????N-?O-???????www.cbs.dtu.dk/services
  /NetNGlyc?www.cbs.dtu.dk/services/NetOGlycO-?????
  www.cbs.dtu.dk/databases/OGLYCBASE (g)
  ?????http//afmb.cnrs-mrs.fr/CAZY

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7,???????

• http//www.ccrc.uga.edu/
• (University of Georgia Complex Carbohydrate
  Research Center)
• http//www.glycominds.net
• http//www.glycosciences.de (German Cancer
  Research Center Heidelberg, ??SweetDB?????? )