Chemistry Reference
In-Depth Information
Info Box 2
'An early observation of Landsteiner had established that for artifi cial antigens
a simple substance with a structure closely related to, or identical with, the
immunologically determinant (haptenic) group of the antigen can combine
with the antibody and thereby competitively inhibit the reactions between
antigen and antibody. Although this principle is employed today in many forms
of inhibition tests, in the 1950s it had not been used to fi nd the determinants
in naturally occurring antigens. By 1952 we had accumulated a large selection
of anti-H reagents of human and animal origin and we decided, with no great
expectation of the outcome, to screen them for inhibition of the agglutination
of 0 cells with the component sugars present in the blood- group active sub-
stances. Somewhat to our surprise one of the many reagents, that from the eel,
Anguilla anguilla,
was quite strongly inhibited by
L
-fucose and to a greater extent
by
- methyl
L
-fucoside and not by the other monosaccharides. Our conclusions
were somewhat tentative at fi rst because this was an isolated result with a rather
exotic reagent, but the inference that
L
- fucose in
α
- linkage is more important
than the other sugars for H specifi city was reinforced when we were given some
plant agglutinins (later called lectins)…' [W.M. Watkins. A half century of blood-
group antigen research: some personal recollections.
Trends Glycosci Glycotech-
nol
1999;
11
, 391-411; for illustration of the folding of the eel agglutinins, please
see Figure 16.1 g].
α
a common feature of
N
- and
O
-glycan structures (please see Chapters 6 - 8 ), and
has a bearing on bioaffi nity in receptor (lectin) binding [2]. Consideration of the
factors of sequence, of linkage- point and ring -size permutations as well as branch-
ing sets glycans far apart from nucleic acids and proteins in terms of coding
capacity. In actual numbers, only 4096 (4
6
) hexanucleotides are possible with the
four letters in the DNA language and still 6.4
10
7
(20
6
) hexapeptides from 20
proteinogenic amino acids, but the staggering number of 1.44
×
10
15
hexasaccha-
rides from 20 monosaccharides [3]. Even though not every combination is realized,
since oligomer synthesis is confi ned to using exclusively the anomeric center of
the activated donors (please see also Table 1.1), the case for an enormous potential
×
Figure 1.5
Illustration of the linkage pattern in
ABH(0) histo - blood group tri - and tetrasaccha-
rides. The core H(0)-trisaccharide (type I:
by either
N
- acetylgalactosamine (A epitope) or
galactose (B epitope). A branched structure is
generated, as intimated by arrows in Figure 1.3.
For structures of the individual 'letters' of the
ABH(0) ' words ' , please see Figure 1.6 .
α
1 - 2 -
fucosylated Gal
p
1 - 3GlcNAc
p
), whose
L
- fucose
part is freely accessible to the eel lectin (please
see Info Box 2), can be extended in
β
α
1,3 - linkage
