Introduction
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ROGER W. JEANLOZ Laboratory for Carbohydrate Research, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114
To some chemist members of the Division of Carbohydrate Chemistry of the American Chemical Society, which is organizing this symposium, it may be unexpected that, for the next few days, we w i l l be discussing compounds that encompass lipids and proteins, in addition to carbohydrates, and their relation to disease processes. It is within the life span of many of us that natural product chemists have realized that nature is not compartmentalized into such nice and clean-cut categories as carbohydrates, proteins, and l i p i d s ; in fact, very few carbohydrates exist that are devoid of a peptide or l i p i d component, as well as there are few proteins devoid of a carbohydrate component. The roles of the carbohydrate component, of glycoproteins and glycolipids that are located at the surface of the animal c e l l or present in the connective tissue that links the c e l l s , have received increased recognition in the past decade and w i l l be discussed during the next few days. The subjects of the f i r s t session of this symposium w i l l be the methods of structure identification presently being developed, as well as the biosynthesis and degradation of glycoproteins and glycolipids. Because glycoproteins and glycolipids of biological interest are generally available only in minute amounts, the methods of structure identification, which w i l l be discussed by Dr. Walborg in his general presentation of current concepts of glycoprotein structure, are being developed at the micro- and even nano-gram l e v e l . Dr. Schachter and associates w i l l entertain us with the very active development of glycoprotein biosynthesis presently taking place. For many years, the concept of glycoprotein and glycolipid biosynthesis was dominated by the concept of elongation of the chains by one carbohydrate unit at a time, through sugar nucleotides; this concept, f i r s t developed for such homoglycans as glycogen and starch, was very ably demonstrated for glycoproteins and glycolipids by Roseman's group. Nearly twenty years ago, this unified concept of chain elongation was shown to be invalid for bacterial polysaccharides, and the importance of isoprenoid 3 © 1978 American Chemical Society In Glycoproteins and Glycolipids in Disease Processes; Walborg, E.; ACS Symposium Series; American Chemical Society: Washington, DC, 1978.
4
GLYCOPROTEINS AND GLYCOLIPIDS IN DISEASE PROCESSES
sugar
phosphate
recognized. work
on
sugar have in
the
intermediates
years in
the
D-glucose
etc.
It
with
the
glycoprotein
is
of
of
more
the
than
polysaccharide group,
established
in
the
the
role
role
component
the
passing
of of
transfer interest
processes:
One
^-glycoproteins
and
involves
rather
where
the
carbohydrate
takes
place
through
at
l i p i d
elongation, are
The which
of
their
these
be
to
as
blood-group
simple
components
two
discussed
length
to
few
years
intermediates
the
chain,
are
faced
now
in
animal
and
mechanism,
peptide
backbone
synthesized
degraded
before
where
sugar
the
peptide
complex
coexist
by
Dr.
those
of
only
up
to
surface
result
(for
new
sugar
units
nucleotides.
or
are
Time
merely
of
have
and
the
of
the
a-D-galacto-
chain
has
cells
of
been
glycolipids), chains
of
reported),
during
the
specific
genetic
defects,
a l l
reasons
for
been
his
organisms,
carbohydrate
units
the
and
glycosphingolipids.
example
for
50
Sweeley
eukaryotic
within
(evidence
having
typing,
past
experimentation.
found
the
we
process
from
processes
structures
are
at
the
very
the
active
to
glycoglycerolipids
their
chain
units
its
^-glycoproteins,
oligosaccharides
and p a r t i a l l y
a
be
solely
of
variation or
large
restricted
composition
process
is
single
residues
their
complex
in
w i l l
encompass
of
of
inadequate
diversity
pyranosyl and
as
glycolipids
associates The
second
show w h e t h e r
expression
stage
intermediates
the
transferred
w i l l
of
the
a
is
was
for
isoprenoid
The
that
two
transfer
of
known
these
to
of
synthesis
already
biosynthesis.
of
core
residues
existence
in
L e l o i r ' s
development
biosynthesis
of
ago,
nucleotides,
phosphates
plant
Downloaded by PENNSYLVANIA STATE UNIV on June 8, 2012 | http://pubs.acs.org Publication Date: June 1, 1978 | doi: 10.1021/bk-1978-0080.ch001
sugar
witnessed
role
as
Ten
oncogenic their
active
role
investiga
tion. Finally, the
most
microgram
specific chains
the
by
ago,
Dr.
of
we
by
were
Maley
Eylar of
D.
not
Dr.
degradation
methods the
identification of
this
his
been
are
we
and to
of
It
able
the the
more
progresses
glycoproteins these
to
my
the
I
laboratory structure such
that
present
addition of established and
structures
of
α -acid an
glycolipids disease
endo-
found
extract
that
biochemical
chemical i n
glyco
x
of
the
25
exo-
enzyme, in
be
when,
with
lack
such
recently
with
carbohydrate
remember
time
made
off
at
the
and which w i l l
the
was
elucidations
without
s p l i t
linkage
deploring
group,
is
the
in
on
were
his
structure possible
associates.
working
pneumoniae
great
correlation of
subject
was
manipulating.
allowed
chemical
have
that
r e a l i z i n g at
Kobata
has the
not
and
human p l a s m a ,
glycosidase later
recent
carbohydrate-peptide
Dr.
glycosidases protein
the would
endo-glycosidases
near
discussed years
of
level
methods
that
structural
and
made
possible
processes,
Symposium.
RECEIVED August 2, 1978.
In Glycoproteins and Glycolipids in Disease Processes; Walborg, E.; ACS Symposium Series; American Chemical Society: Washington, DC, 1978.
the
