Ram Sasisekharan, James R. Myette
The Sweet Science of Glycobiology
Complex carbohydrates, molecules that are particularly important for communication
among cells, are coming under systematic study
Carbohydrates are the often-overlooked third major class of biological polymers. Though they have
received much less notice than nucleic acids or proteins, they are just as essential for life. Complex
sugars, or glycans, which are generally bound to proteins, coat the outsides of cells and fill the
spaces between them. Crucial in normal animal development and in preventing many diseases,
glycans appear to act as scaffolds that mediate interactions between proteins. The authors describe
the progress made recently in identifying or "sequencing" polysaccharides, in understanding their
functions and in beginning to exploit them in medicine.
The Sweet Science of Glycobiology
Complex carbohydrates, molecules that are particularly important for communication
among cells, are coming under systematic study
Carbohydrates are the often-overlooked third major class of biological polymers. Though they have
received much less notice than nucleic acids or proteins, they are just as essential for life. Complex
sugars, or glycans, which are generally bound to proteins, coat the outsides of cells and fill the
spaces between them. Crucial in normal animal development and in preventing many diseases,
glycans appear to act as scaffolds that mediate interactions between proteins. The authors describe
the progress made recently in identifying or "sequencing" polysaccharides, in understanding their
functions and in beginning to exploit them in medicine.
Mark M. Fuster; Jeffrey D. Esko
The Sweet and Sour of Cancer: Glycans as Novel Therapeutic Targets
Nat Rev Cancer. 2005;5(7):526-542. ©2005 Nature Publishing Group
Posted 07/25/2005
Abstract
A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of
tumour progression. Glycans regulate tumour proliferation, invasion, haematogenous metastasis
and angiogenesis, and increased understanding of these roles sets the stage for developing
pharmaceutical agents that target these molecules. Such novel agents might be used alone or in
combination with operative and/or chemoradiation strategies for treating cancer.
To read full text article, you will need to sign in to medscape
The Sweet and Sour of Cancer: Glycans as Novel Therapeutic Targets
Nat Rev Cancer. 2005;5(7):526-542. ©2005 Nature Publishing Group
Posted 07/25/2005
Abstract
A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of
tumour progression. Glycans regulate tumour proliferation, invasion, haematogenous metastasis
and angiogenesis, and increased understanding of these roles sets the stage for developing
pharmaceutical agents that target these molecules. Such novel agents might be used alone or in
combination with operative and/or chemoradiation strategies for treating cancer.
To read full text article, you will need to sign in to medscape
Other Links and Resources
| Glycobiology is a new field of science that combines the expertise of both carbohydrate (sugar) biochemistry and molecular biology. Involved is the study of the structure, chemistry, biosynthesis, and biological functions of glycans and their derivatives. |
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Joseph R. Bishop, Manuela Schuksz, Jeffrey D. Esko
Heparan sulphate proteoglycans fine-tune mammalian physiology
Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far
and are a major component of extracellular matrices. Studies of model organisms and human
diseases have demonstrated their importance in development and normal physiology. A recurrent
theme is the electrostatic interaction of the heparan sulphate chains with protein ligands, which
affects metabolism, transport, information transfer, support and regulation in all organ systems.
The importance of these interactions is exemplified by phenotypic studies of mice and humans
bearing mutations in the core proteins or the biosynthetic enzymes responsible for assembling the
heparan sulphate chains.
SUMMARY: Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells
studied so far and are a major component of extracellular matrices. Studies of model organisms and
human diseases
CONTEXT: hereditary multiple exostoses, an autosomal dominant disease characterized by the
formation of cartilage-capped bony outgrowths (osteochondromas or exostoses) on growth plates
throughout the body. Heterozygous mice also develop...
Nature 446, 1030 - 1037 (25 Apr 2007) Insight
Heparan sulphate proteoglycans fine-tune mammalian physiology
Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells studied so far
and are a major component of extracellular matrices. Studies of model organisms and human
diseases have demonstrated their importance in development and normal physiology. A recurrent
theme is the electrostatic interaction of the heparan sulphate chains with protein ligands, which
affects metabolism, transport, information transfer, support and regulation in all organ systems.
The importance of these interactions is exemplified by phenotypic studies of mice and humans
bearing mutations in the core proteins or the biosynthetic enzymes responsible for assembling the
heparan sulphate chains.
SUMMARY: Heparan sulphate proteoglycans reside on the plasma membrane of all animal cells
studied so far and are a major component of extracellular matrices. Studies of model organisms and
human diseases
CONTEXT: hereditary multiple exostoses, an autosomal dominant disease characterized by the
formation of cartilage-capped bony outgrowths (osteochondromas or exostoses) on growth plates
throughout the body. Heterozygous mice also develop...
Nature 446, 1030 - 1037 (25 Apr 2007) Insight
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Heparan Sulfates - Regulators of Cell Functions
Heparan sulfates (HS): are glycans (complex
sugars) found on all cell surfaces which act by
binding selectively to a variety of proteins and
pathogens and are critically relevant to many
disease processes (eg. , inflammation,
neurodegeneration, angiogenesis, wound healing,
cancer, cardiovascular disordersand infectious
diseases). Many of these activities have been
detected using heparin, which is a subclass of the
HS family of glycans .
Heparan sulfates (HS): are glycans (complex
sugars) found on all cell surfaces which act by
binding selectively to a variety of proteins and
pathogens and are critically relevant to many
disease processes (eg. , inflammation,
neurodegeneration, angiogenesis, wound healing,
cancer, cardiovascular disordersand infectious
diseases). Many of these activities have been
detected using heparin, which is a subclass of the
HS family of glycans .
Heparin and heparan sulphates act by binding to
proteins and regulating their biological activities.
The picture shows the interaction of a small heparin
hexasaccharide (6 sugar units) with the growth
factor called basic FGF that controls the growth and
differentiation of many cell types.
The HS family of sugars are composed of long
chains of repeating disaccharide units of uronic acid
and glucosamine residues, decorated by variable
patterns of sulphate and carboxyl groups, giving
them very strong negative charge.
They are produced in living cells by a complex
multi-step enzymatic biosynthetic process.
Heparin is a highly sulphated and relatively
structurally homogenous molecule compared to
cellular heparan sulphates, which have increased
sequence diversity and fulfil many complex biological
functions by interacting with proteins and
influencing their biological activities.
chains of repeating disaccharide units of uronic acid
and glucosamine residues, decorated by variable
patterns of sulphate and carboxyl groups, giving
them very strong negative charge.
They are produced in living cells by a complex
multi-step enzymatic biosynthetic process.
Heparin is a highly sulphated and relatively
structurally homogenous molecule compared to
cellular heparan sulphates, which have increased
sequence diversity and fulfil many complex biological
functions by interacting with proteins and
influencing their biological activities.
Animated picture shows an extended helical
heparin sequence with sulphate groups
(yellow/red) decorating the backbone
(image courtesy of Dr Barbara Mulloy,
National Institiute of Biological Standards,
Herts, UK)
heparin sequence with sulphate groups
(yellow/red) decorating the backbone
(image courtesy of Dr Barbara Mulloy,
National Institiute of Biological Standards,
Herts, UK)
HS and heparin are produced on cells by a
complex process involving the sequential action
of multiple enzymes which knit together the
repeating disaccharide units (polymerases) and
then modify them with exquisitely complex
patterns of sulphate groups
(sulfotransferases). The resulting structural
motifs bind to specific proteins and influence
their biological activities.
complex process involving the sequential action
of multiple enzymes which knit together the
repeating disaccharide units (polymerases) and
then modify them with exquisitely complex
patterns of sulphate groups
(sulfotransferases). The resulting structural
motifs bind to specific proteins and influence
their biological activities.
Heparan sulphate binds proteins
Heparin and heparan sulphates act by binding to
proteins and regulating their biological activities.
The picture shows the interaction of a small
heparin hexasaccharide (6 sugar units) with the
growth factor called basic FGF that controls the
growth and differentiation of many cell types.
Heparin and heparan sulphates act by binding to
proteins and regulating their biological activities.
The picture shows the interaction of a small
heparin hexasaccharide (6 sugar units) with the
growth factor called basic FGF that controls the
growth and differentiation of many cell types.
heparan sulfate proteoglycans (HSPGs), are ubiquitous glycoproteins present at the cell surface and
in the extracellular matrix, and have their roles in neuron migration, process outgrowth and guidance
and in synapse formation. HSPGs contain a protein core substituted with heparan sulphate (HS)
polysaccharide chains, which encode complex sugar sequences with variant sulfation patterns that
confer biological functions as protein regulators. HS/HSPGs play essential roles in controlling cell
differentiation, tissue morphogenesis and homeostasis. In the nervous system, HS and HSPGs have
been implicated in neuron migration, axon guidance, synapse formation and maturation and control
of physiological responses such as feeding, learning and memory.
in the extracellular matrix, and have their roles in neuron migration, process outgrowth and guidance
and in synapse formation. HSPGs contain a protein core substituted with heparan sulphate (HS)
polysaccharide chains, which encode complex sugar sequences with variant sulfation patterns that
confer biological functions as protein regulators. HS/HSPGs play essential roles in controlling cell
differentiation, tissue morphogenesis and homeostasis. In the nervous system, HS and HSPGs have
been implicated in neuron migration, axon guidance, synapse formation and maturation and control
of physiological responses such as feeding, learning and memory.
HS/heparin structure
HS and heparin are long, linear chains of
sugars, composed of repeating disaccharide
units made up of alternating uronic acid
(glucuronic or iduronic acid) and glucosamine
residues. The backbone structure is then
decorated with complex patterns of sulphate
groups at various positions.
HS and heparin are long, linear chains of
sugars, composed of repeating disaccharide
units made up of alternating uronic acid
(glucuronic or iduronic acid) and glucosamine
residues. The backbone structure is then
decorated with complex patterns of sulphate
groups at various positions.
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sciences a free online service providing access to the very best Web resources for education and research
located in the UK
By the Health On the Net Foundation. Click here to verify.# HON Conduct 282463 and is linked on the NIH
National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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The information provided here is for educational and informational purposes only. This website does not engage in the practice
of medicine. In all cases we recommend that you consult your own physician regarding any course of treatment or medicine.
The MHE Research Foundation is proud to be an affiliate of the Society For Glycobiology