Download CARBOHYDRATES B: Polysaccharides Learning Goals/Objectives

CARBOHYDRATES
B: Polysaccharides
Learning Goals/Objectives for Chapter 3B: After class and this reading, students will be able to
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state the differences between the homopolysaccharides glycogen, starch cellulose, and
chitin and those with dissacharide repeat units (glycosoaminoglycans)
draw cartoon models of complex oligosaccharides such as peptidoglycans of bacterial
cell walls, N and O linked glycogproteins, and proteoglycans showing the linkage of
protein and CHO
describe the role of protein and cell surface CHO in binding and biological function
given diagrams of leukocyte and endothelial cells interactions, describe the role of
selectins, selectin ligands, integrins and cellular adhesion molecules in immune cell/blood
vessel interactions.
This chapter on carbohydrates will review those features that are deemed especially
important for a one semester course dealing with structure and function of
biomolecules.
Polysaccharides
These contain many monosaccharides in glycosidic links, and may contain many
branches. They serve as either structural components or energy storage molecules.
The most common polysaccharides consisting of single monosaccharides are:
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starch (found in plants). It's a polymer of Glc linked in a main chain through  1>4 links with  1->6 branches. Amylose is starch with no branches, while
amylopectin has branches. Starch granules consist of about 20% amylose and
80% amylopectin.
glycogen, the main CHO storage in animals. Muscle and liver glycogen consists
of Glc residues in  1->4 links with lots of  1->6 branches (many more branches
than in starch). The polymer is synthesized on a protein primer called
glycogenin (G), and has a structure shown below (in which only 5 rings of the
structure are shown instead of the actual 12. (Meléndez-Hevia et al. )
dextran is a branched polymer of glucose in  1->6 links with  1->4 branches
and is used in Sephadex chromatography beads.
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celluose, a structural Glc polymer in plants, consists of  1->4 links. It is held
together by intra and inter-chain H-bonds. It is the most abundant biological
molecule in nature.
chitin, the major substance in exoskeletons of anthropods and mollusks is a  1>4 linked polymer of GlcNAc.
The basic chemical structures of these homopolymers are shown below.
Homopolysaccharides in Chair Conformations
Glc  (1-4) Glc link
It makes great chemical sense to store Glc residues as either glycogen or starch, which
is one large molecule. A review of colligative properties would inform you that if all the
Glc was stored as the monosaccharide, a great osmotic pressure difference would be
found between the outside and inside of the cell. It makes more sense to have
glycogen exist as a many-branched linear polymer. When Glc is needed, it is cleaved
one residue at a time from all the branches (at the nonreducing ends), producing a large
amount of free Glc in a short time.
Phi/Psi angles can also be described for the starch/glycogen main chain (around the
acetal O) in a fashion comparable to that for proteins (around the alpha carbon). The
phi torsion angle describes rotation around the C1-O bond of the acetal link, while the
psi angle describes rotation around the O-C4 bond of the same acetal link, with the
glucopyranose ring considers as a rigid rotator (just as the 6 atoms in the planar peptide
bond unit). The most extended form of a Glcn polymer occurs when the glycosidic link
is 1->4 (as in cellulose), which forms linear chains. The  1->4 linked main chain of
glycogen and starch causes the chain to turn and form a large helix, into which can fit
iodine (or I3-), which turns starch purple.
Jmol: Glycogen
cellulose
Jmol: Amylose
Jmol: Amylopectin
Jmol:
Many polysaccharides consist of repeating dissacharides units. Agarose, a polymer of
a disaccharide repeat of (1-->3)-β-D-galactopyranose-(1 --> 4)-3,6-anhydro-α-Lgalactopyranose, is often used for a gelable solid phase for electrophoresis of nucleic acid and as
a component of chromatography beads. A major class of polysaccharides with
dissacharide repeats include the following glycosoaminoglycans (GAGs), all which
contain one amino sugar in the repeat and in which one or both of the sugars contain
negatively charged sulfate or carboxyl groups. The extent and position of sulfation
varies widely between and within GAGs.
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hyaluronic acid, a polymer of Glucuronate ( 1->3) GlcNAc
dermatan sulfate, L-iduronate ( 1->3 ) GalNAc-4-sulfate
keratan sulfate, D-Gal ( 1->4) GlcNAc-6-sulfate
chondrotin sulfate, D-glucuronate ( 1->3) GalNAc-4 or 6-sulfate
heparin - D-glucuronate-2-sulfate ( 1->4) GlcNSulfo-6-sulfate
GAGs are found in the vitreous humor of the eye and synovial fluid of joints, and in
connective tissue like tendons, cartilage, etc, as well as skin. They are found in the
extracellular matrix and are often covalently attached to proteins to form
proteolglycans.
Chime: Chondrotin Sulfate
Chime: Glycobiology resources: GAGs
A New visual nomenclature for glycobiology
A new symbolic nomenclature for carbohydrates in which monosaccharides are denoted
by specific colored geometric shapes has been proposed by the Consortium for
Functional Glycomics (2005). An example is shown below. This chapter is being
slowly updated to reflect these changes.
Figure: CHO symbolic nomenclature
COMPLEX OLIGOSACCHARIDE DERIVATIVES
1. Cell Membranes of Bacteria
In contrast to eukaryotic cells, bacteria cells have a cell wall in addition to a lipid bilayer
membrane. These are essentially carbohydrate polymers which offer protection from
exterior hypotonic condition and the high internal osmotic pressures, preventing swelling
and bursting of the cells. The membrane consist of a peptidoglycan. Two types exists.
a. Gram positive bacteria- These bacterial can be stained with Gram stain. The wall
consists of a GlcNAc ( 1->4) MurNAc repeat . This is similar to the GlcNAc ( 1->4)
GlcNAc homopolymer chitin, except that every other GlcNAc contains a lactate
molecule covalently attached in an ether-linkage to the C3 hydroxyl to form the
monomer N-Acetylmuramic acid. A tetrapeptide (Ala-D-isoGlu-Lys-D-Ala) is attached
in amide link to the carboxyl group of the lactate in MurNAc. The GlcNAc ( 1->4)
MurNAc strands are covalently connected by a pentaglycine bridge through the epsilon
amino group of the tetrapeptide Lys on one strand and the D-Ala of a tetrapeptide on
another strand.
One final structure is found in Gram + membranes. Techioic acids are often attached to
the C6 of MurNAc. Teichoic acid is a polymer of glycerol or ribitol to which alternative
GlcNAc and D-Ala are linked to the middle C of the glycerol. Multiple glycerols are
linked through phosphodiester bonds. These teichoic acids often make up 50% of the
dry weight of the cell wall, and present a foreign (or antigenic) surface to infected hosts.
These often serve as receptors for viruses that infect bacteria (called bacteriophages).
Jmol: Peptidoglycan glycosyl transferase
b. Gram negative bacteriaThese bacterial can NOT be stained with Gram stain. The wall consists of the same
structure as in Gram positive bacteria, but the GlcNAc ( 1->4) MurNAc strands are
covalently connected through a direct amide bond between the epsilon amino group of
the tetrapeptide Lys on one strand and the D-Ala of a tetrapeptide on another strand.
(i.e. no pentaGly spacer). In addition, Gram negative bacterial don't have teichoic acid
polymers. Rather they have a second, outer lipid bilayer. The cell wall is sandwiched
between the inner and outer bilayers. The space between the lipid bilayers is called the
periplasmic space. A hydrophobic protein covalently attaches (through an amide link
from a protein Lys) to the cell wall at the last amino acid in the tetrapeptide unit of the
wall (actually diaminopimelic acid which replaces about 10% of the D-Ala in the cell
wall). The N-terminal of the hydrophobic proteins attaches to the outer lipid membrane
through a Ser. The outer membrane is coated with a lipopolysaccharide (LPS) of
varying composition. The LPS determines the antigenicity of the bacteria. The different
LPS are called the O-antigens.
Figure: A detailed view of LPS
2/18/10:Figure: Heteropolysaccharides in Chair Conformations
2. Glycoprotens
Many proteins, especially those destined for secretion or insertion into membranes, are
post-translationally modified by attachment of carbohydrates. They are usually attached
through either Asn or Ser side chains. Carbohydrate modifications on the protein appear
to be involved in recognition of other binding molecules, prevention of aggregation
during protein folding, protection from proteolysis, and increases half-life of the proteins.
In contrast to a protein sequence which is determined by a DNA template, sugars
are attached to proteins by enzymes which recognize appropriate sites on
proteins and attach the sugars. Since there are many sugars which contain many
functional groups that can serve as potential attachment sites, the structures of
the oligosaccharides attached to proteins are enormously varied, complex, and
hence "information rich" compared to linear or folded polymers like DNA and
proteins.
a. N-linked Glycoproteins
These contain CHOs attached through either a GlcNAc or GalNAc to an Asn in a X-AsnX-Thr sequence of the protein. There are three types of N-linked glycoproteins, high
mannose, complex, and hybrid. They all contain the same core oligosaccharide (Man)3(GlcNAc)2 attached to Asn.
Figure: N-linked high mannose glycoproteins
Figure: N-linked complex glycoproteins
Figure: N-linked hybrid glycoproteins
Note that in the hybrid oligosaccharide, one terminus contains Gal(-1,4)GlcNAc.
However, in all other mammals except man, apes, and old world monkey, an additional
Gal is often connected in an -1,3 link to the Gal to give a terminus of: Gal(-1,3)Gal(1,4)GlcNAc. These animals have an additional enzyme, -1,3 Gal transferase.
Bacteria also have this enzyme and since we have been exposed to this link through
bacterial infection, we mount an immune response against it. Why is this important?
Pig hearts turn out to be similar to human hearts, so they might be good candidates for
transplantation into humans (xenotransplants). However, the Gal--1,3-Gal link is
recognized as foreign, and we mount a significant immune response against it. Several
biotech firms are trying to delete the pig -1,3 Gal transferase which would prevent the
addition of the terminal Gal, and make them good donors for transplanted hearts.
Chime: N-Linked Complex CHOs
Influenza and the Avian Flu
The influenza virus is a simple yet deadly virus (shown below) . It interacts with human
cells through a surface protein, hemagglutinin (HA).
credit: © Paul Digard, Dept Pathology, University of Cambridge
http://www-micro.msb.le.ac.uk/3035/Orthomyxoviruses.html
The virus binds to host cells through interaction of HA with cell surface carbohydrates. Once
bound the virus internalizes, ultimately leading to release of the RNA genome of the virus
into the host cell.
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Animation: Influenza entering cell
The hemagglutin protein is the most abundant protein on viral surface (as surmised by
antibody formation). 15 avian and mammalian variants have been identified (based on
antibody studies). Only 3 adapt to humans in last 100 yr, giving pandemic strains H1
(1918), H2 (957) and H3 (1968) . 3 recent avian variants (H5, H7, and H9) jump directly
to humans recently but have low human to human transmissibility.
The influenza hemagglutinin protein has the following characteristics:
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mature form is homotrimer (3 identical protein subunits), MW 220,000; multiple
sites for covalent attachment of sugars. Hemagglutinin is a glycoprotein.
each monomer synthesized as single polypeptide chain precursor (HA0) that is
cleaved into HA1 and HA2 subunits by the protease trypsin in epithelial cells of lung.
structure known for human (H3), swine (H9), avian (H5) subtypes.
Chime: Hemagglutinin antigen
Hemagluttinin bind to sialic acid (Sia), which is covalently attached to many cell
membrane glycoproteins. The sialic acid is usually connected through an (2,3) or (2,6)
link to galactose on N-linked glyocproteins. The subtypes found in avian (and equine)
influenza isolates bind preferentially to Sia (2,3) Gal which predominates in avian GI tract
where viruses replicate. Human influenza isolates prefer Sia (2,6) Gal. Human virus of
H1, H2, and H3 subtype (cause 1918, 1957, and 1968 pandemics) recognize Sia (2,6)
Gal, major form in human respiratory tract. The swine influenza HA bind to Sia (2,6) Gal
and some Sia (2,3) Gal both of which found in swine.
Sia (2,6) Gal (Human)
(made with Sweet, with an OH, not AcNH on sialic acid
on C5)
Sia (2,3) Gal (Avian and some Swine)
(made with Sweet, with an OH, not AcNH on sialic acid
on C5)
Structures from: http://www.bme.jhu.edu/~kjyarema/CellSurCarbo1.htm#linkages
The present avian flu (H5N1) is deadly but lacks human to human transmissibility at the
moment. Why? One reason is that it appears to bind deep in the lungs and is not released
easily on coughing or sneezing. It appears that cell surface glycoproteins deeper in the
respiratory tract have Sia (2,3) Gal which accounts for this pathology.
The virus, before it leaves the cell, forms a bud on the intracellular side of the cell with the
HA and NA in the cell membrane of the host cell. The virus in this state would not leave the
cell since its HA molecules would interact with sialic acid residues in the host cell
membrane, holding the virus in the membrane. Neuraminidase hydrolyzes sialic acid from
cell surface glycoproteins, allowing the virus to complete the budding process and be
released from the cell as new viruses. The drugs Oseltamivir (Tamiflu) and zanamivir
(Relenza) bind to and inhibit neuraminidase, whose activity is necessary for viral release
from infected cells. Tamiflu appears to work against N1 of the present H5N1 avian influenza
viruses. Governments across the world are stock piling this drug in case of a pandemic
caused by the avian virus jumping directly to humans and becoming transmissible from
human to human.
Jmol: Oseltamivir: Neuramindase N1 complex.
b. O-linked Glycoproteins
The CHOs are usually attached from a Gal ( 1-3) GalNAc to a Ser or Thr of a protein.
The blood group antigens (CHOs on cells attached to either proteins or lipids) are
examples .
3. Proteoglycans - PGs
Some proteins are so modified with CHOs that they contain more CHOs than amino
acids. Proteins linked to glycosoaminoglycans are together called proteoglycans. (PGs)
The structure of a few proteoglycans is known. The GAGs are O-linked to the protein
typically to a Ser of a Ser-Gly dipeptide often repeated in the protein. Some of the
proteoglycans also contained N-linked oligosaccharide groups.
PGs can be soluble and found in the extracellular matrix, or as integral membrane
proteins. Given the diversity of sugars and the varying extent of sulfation, the CHO part
of PGs provide an incredible vary of binding structures to at or near the cell surface.
One PG, syndecan, binds through its intracellular domain to the internal cytoskeleton of
the cell, while interacting with another protein - fibronectin - in the extracelluar matirx.
Fibronectin also binds other molecules which can regulate cellular growth and other
interactions. PGs act like glue in connecting the extracellular and intracellular functions
of the cell. Most proteins bind PGs through a PG binding motif of BBXB or BBBXXB
where B is a basic amino acid. Some proteins bind to specific sequences in specific
GAGs. For instance, antithrombin 3, an inhibitor of blood clotting, binds specifically to
heparin, which enhances its interaction with the clotting protein thrombin.
4. Cell Membranes of Eukaryotes
We have studied lipids, proteins, and carbohydrates. Although phospholipid can
spontaneously form biliayers, the actual structure of biological membranes is made
much more complicated through addition of protein and carbohydrate substituents to the
membrane.
Normally, soluble proteins can be made to insert into bilayers by addition of nonpolar
attachments. Several examples of such attachments include:
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N-myristoylation (attached myristic acid - 14:0 - through an amide link)
S-palmitoylation (attach palmitic acid - 16:0 - through a thioester link with a Cys
farnesyl or geranylgeranyl additon to a CAAX carboxy-terminal sequence in a
target protein, where C is Cys, A is aliphatic, and X is any amno acid
addition of a protein to a glycosyl phophatidylinositol (GPI), through a complex
which usually contains a conserved tetrasaccharide core of 3 Man and 1 GlcNAc
residues linked to a protein. The GPI can be further modified with extra Gal's and
Man, as well as additions to the PI group, which secures the protein in the
membrane. GPIs are found in eukaryotic cells, and link many surface antigens,
adhesion molecules, and hydrolases to the membrane. GPIs from Plasmoidium
falciparum, the malarial parasite which kills about two million people each year,
appears to act as a toxin and is the most common CHO modification of the
parasite protein. Mice immunized against the GPI sequence, NH2-CH2-CH2-PO4Man 1-2) 6Man 1-2) Man 1-6) Man 1-4) GlcNH2 (1-6) myo-inositol-1,2cyclic-phosphate, were substantially protected from malarial symptoms and death after
they were exposed to the actual parasite.
Figure: Biological Membranes: Simple to Complex
Figure: A cool view of a membrane surface
Role of Cell Surface Carbohydrates
Cell surface carbohydrates present information-rich binding sites for other molecules
and act as "receptors" for biological agents as diverse as viruses, bacteria, toxins, and
other cells. This is illustrated well by studying the properties of circulating immune
cells. The cells must often pass through the walls of capillaries as they hone in on a site
of infection. (Cancer cells do this as well as they escape the boundaries of the organ in
which they developed and pass through the blood vessels and into new tissues in the
process of of forming metastases.) Immune cells must first bind to endothelial cells (a
monolayer of cells that line the lumen of the blood vessels) before they can pass
through the vessel walls. Proteins called selectins our found on cells that can pass
through vessels and on endothelial cells. There are 3 types:
1. L-selectins: found on leukocytes ("white" blood cells that are circulating immune
cells)
2. P-selectins: found on activated platelets (which can aggregate to form a type of
blood clot) and activated endothelial cells. Activation occurs during the
inflammatory response can to the quick movement of pre-formed selectins stored
within the cytoplasm. In addition, their expression can be induced.
3. E-selectins: found on activated endothelial cells only after the cells have been
induced to form them by certain immune hormones called cytokines releases by
immune cells during an inflammatory response.
These selectins are transmembrane proteins with an extracellular CHO binding domain,
an EGF-like (epidermal growth factor like) domain, varying numbers of C (complement
regulatory) domains, and a transmembrane domain. The extracellular CHO binding
domain is found in proteins in all organisms. Proteins that bind that bind carbohydrate
motifs are called lectins.
Lectins and CHO ligands
Lectin Family/Lectin
Abbreviation
Plants
Concanavilin A
ConA
Griffonia simplicifolia lectin 4 GS4
Wheat germ agglutinin
Ligand(s)
Man1-OCH3
Lewis b (Leb) tetrasaccharide
Ner5Ac(2->3)Gal(1>4)GlcGlcNAc(1->4)GlcNAc
Gal(1->4)Glc
WGA
Ricin
Animals
Galectin-1
Mannose-binding protein
Gal(1->4)Glc
High Mannose Octasaccahride
MBP-A
Viral
Influenza Virus hemagglutinin HA
Polyoma virus protein 1
VP1
Neu5Ac(2->6)Gal(1->4)Glc
Neu5Ac(2->3)Gal(1->4)Glc
Bacterial
Enterotoxin
Cholera toxin
LT
CT
Gal
GM1 pentasaccharide
In animals, lectins facilitate cell-cell interactions by forming multiple, but weak
interactions between the protein and many sugars on the ligand to which it binds.
The selectins are also part of a class of molecules called adhesion molecules. As
mentioned for the selectins, adhesion molecules contain
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an extracellular CHO binding domain (the lectin domain), which mediates binding
to adjacent cells or to the extracellular matrix; The P, L, and E selectins can bind
a tetrasaccharide containing Sia-Gal-GalNAc-Fuc (called sialyl-Lewisx) on
selectin ligand proteins and glycolipids.
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a transmembrane domain;
and a cytoplasmic domain which often interacts with the cytoskeleton within the
cell.
The selectins recognize Ser-linked CHO residues (a tetrasaccharide containing sialic
acid, galactose, fucose, and GalNAc) displayed on transmembrane glycoproteins called
selectin ligands on endothelial cells. L selectins bind to endothelial cell ligands while P
and E selectins bind to ligands on leukocytes. These interactions slow the leukocyte
down as it rolls along the surface of the endothelial cells. These interactions involve
protein-CHO binding.
This initial binding mediated by selectin-CHO interactions activate the expression of
another adhesion molecule on the leukocyte, integrin, a heterodimer with an  and 
chain. These cause strong leukocyte-endothelial cell interactions, leading to ultimate
movement of the leukocytes through the vessel wall. Other classes of adhesion
molecules (in addition to selectins and integrins) are cadherins (calcium-dependent
adhesion molecules), and the immunoglobulin-like superfamily (ICAM1, ICAM2,
VCAM). VCAM (Vascular Adhesion Molecule) binds the integrin expressed on
activated lympocytes, leading to passage of the lympocyte from the lumen of the vessel
into the tissues. Integrins appear to bind proteins in the extracellular matrix through
RGD (Arg-Gly-Asp) and also through LDV (Leu-Asp-Val) motifs on the proteins,
including fibronectin (RGD), thrombospondin (RGD & LDV), fibrinogen (RGD & LDV),
van Willebrand Factor (RGD), vitronectin (RGD). They also bind other matrix proteins
with an "alpha domain" including collagen and laminin. Integrin/Adhesion molecule
interations involve protein/protein interactions.
Genbacev et al. have recently shown that a fertilized egg (in the blastocyst stage which
is ready for implantation in the uterine cell wall) express L-selectin which allows a low
affinity (rolling-type) interaction of the fertiized egg with the uterine epithelial cells.
These cells expressed the CHO ligands on their surface which bind to the L-selectin on
the blastocyst. The CHO ligands are only transiently expressed on the surface of the
epithelial cells of the uterus, presumably only when the uterus is primed for
implantation. After the initial interaction of the blastocyst and epithelial cells, further
expression of integrins on the blastocyst surface might result. Problems in any of these
molecular steps could result in infertility.
Figure: Endothelial Cell/Leukocyte Interactions: Selectins, Integrins, and ICAMs
An interesting experiment was recently done by Davis et al. that showed the importance
of protein modification (like glycoslyslation) to binding and biological function. Posttranslational modifications represent one of natures way to change protein function.
The researchers were able to chemically modify surface features of a protein to produce
new functionalities. They did so by using mutagenesis to change surface amino acids
to Cys or replacing Mets with nonnatural amino acid analogs that contain azide or
alkyne groups. These modified groups could then direct the location of chemical
modifying reagents (such as sugars) to these sites. The researchers studied a pair of
proteins involved in inflammation, P-selectin, which binds a transmembrane protein Pselectin-glycoprotein ligand-1, that requires two post-translational changes to bind to Pselectin. They picked a protein completely unrelated to PSGL-1, and selectively
modified it using this approach so it contain a glycosylated and a sulfated side chain.
The unrelated protein bound to P-selectin.
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Selectins: L-selectin | P-selectin | E-selectin | Selectin Ligands
Integrins at a glance
Integrin: The molecular glue of life
Adhesion Molecules in Biology and Oncology
Inner Life of Cell: from Harvard (wait few moment to load) with narration
Glycobiology resouces: Protein-CHO interactions
Chime: Soybean Agglutinin Lectin
Chime: P-Selectin Lectin/EGF Domains (IG1Q)
Jmol: P-Selectin Lectin/EGF
Domains (IG1Q)
Receptor for Sialic Acids
Lectins that recognize sialic acids, especially members of the Siglec family (sialic acidrecognizing Ig-superfamily lectins) turn out to be important players in our propensity for
disease. As we previously discussed, humans lack a hydroxlase gene necessary for
the hydroxlation of Neu5Ac to Neur5Gc which is found in chimps who possess the
enzyme. Chimp's immune systems seems to confer protection from acquiring simian
version of AIDS, cirrhosis, and other diseases which humans acquire when they are
infected with the human versions of the HIV virus, hepatitis B or C, or other viruses.
These disease and others associated with overactive T cells (rheumatoid arthritis,
asthma, type-I diabetes) are not common in chimps. It turns out that there is a link
between the type of sialic acid and the expresson of siglics that influences the
difference on our disease propensity. Varki et al have shown that chimps and gorillas
show much higher levels of expression of Siglecs on T cells, which are critical
regulatory and effector cells in the immune system. When siglecs on T cells are
activated, T-cell responses are down regulated. Although HIV virus ultimately kills T
helper cells, the virus initially activates them on infection, leading to their proliferation
and production of a larger number of cells for the virus to infect.
Influenza virus that has caused some of the greatest pandemics in world history also
binds to sialic acid on host cells, through a viral binding protein called hemagglutinin.
On binding, conformational changes activate a neuraminidase activity of another viral
protein, allowing cleavage of the sialic acid glycosidic bond, and subsequent entry of the
virus into the cell.
Great CHO Web Sites
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Proteoglycans and Glycosoaminoglycans
Sweet: a program for constructing 3D models of saccharides from their
sequences using standard nomenclature.
Textbook mistakes in Biochemistry: Glycogen
Recent References
1. Sander I. van Kasteren, Holger B. Kramer, Henrik H. Jensen, Sandra J.
Campbell, Joanna Kirkpatrick, Neil J. Oldham, Daniel C. Anthony, Benjamin G.
Davis. Expanding the diversity of chemical protein modification allows posttranslational mimicry. Nature, 446, 1105 (2007).
2. Dzung H. Nguyen, Nancy Hurtado-Ziola, Pascal Gagneux, and Ajit Varki. Loss of
Siglec expression on T lymphocytes during human evolution. PNAS May 16,
2006 vol. 103 no. 20 7765-7770 .
3. Cohen, J. Differences in Immune Cell "Brakes" May Explain Chimp-Human Split
on AIDS. Science 312 672 (2006)
4. Borman, Stu. Carbohydrate Advances. C&E News. August 6, pg 41 (2005).
5. Genbacev, O. , et al. Trophoblast L-Selectin-Mediated Adhesion at the Maternal-Fetal
Interface. Science. 299, pg 405 (2003) (Review: Vol 299, pg 355, 2003)
6. Schfield et al. Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria.
Nature. 418, pg 785 (2002)
7. Samuelson et al. Making Membranes in Bacteria (moving proteins to the correct
location). Nature. 406. pg 575, 637 (2000)
8. Seeberger et al. Sugars Join the Automation rush (sold phase synthesis of
oligosaccharides). Science. 291, pg 805 (2001)
9. Peters et al. Fusion needs more than SNARES (how membranes fuse). Nature
409, pg 567 (2001)
10. Saxon and Bertozzi. Cell Surface Engineering by a modified Staudinger
reaction. Science. 287. pg 2007 (2000)
11. Humprhies et al, Forsberg et al. Mast cell Heparin (role). Nature. 400, pg 714,
769, 773 (1999)
12. Meléndez-Hevia et al. Glycogen Structure: an Evolutionary View", Technological
and Medical Implications of Metabolic Control Analysis (ed. A. Cornish-Bowden
and M. L. Cárdenas), Kluwer Academic Publishers, Dordrecht. pp. 319--326
(2000)
13. Helenius et al. Translocation of lipid-linked oligosaccharides across the ER
membrane requires Rft1 protein. Nature. 415. pg 382, 447 (2002)
Source of Material
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