Chemistry Reference
In-Depth Information
with the corresponding glycans, force-distance curves can be recorded under
physiological conditions. In studies of the Le
x
- Le
x
interaction [20], analysis of
several hundred force curves measured in different areas of the sample indicated
that the specifi c interaction force between two single Le
x
molecules was 20
4 pN.
This value indicates that only fi ve pairs of Le
x
molecules would be necessary to
reach the binding strength (100 pN) between neural retina cells of embryonic
chicken, and 16 Le
x
pairs (320 pN) would be suffi cient to hold T and B lymphocytes
together in the absence of antigen stimulation.
SMFS studies performed with sponge-derived proteoglycans (see Section 21.2.1 )
[1, 7] of their calcium-dependent interactions have revealed functional intermo-
lecular domains that can contribute to many adhesive and elastic extracellular
matrix interactions. Force peaks resulting from g200-g200 glycan interactions in
AFs are separated by an average distance of 20 nm (Figure 21.4), which corre-
sponds to the spacing between g200 glycan anchoring points in the AF. These data
are consistent with a self-adhesion mechanism where each peak in
M. prolifera
AF
force-extension curves corresponds to the breaking of a single g200-g200 interac-
tion. Fitting to a worm-like chain model [33] of the individual peaks (Figure 21.4)
indicates that there is an elastic component involved in the process, probably
resulting from a molecular stretching, before each break of the glycan-glycan
interaction, of the
M. prolifera
AF protein to which g200 is covalently linked. The
multiplicity of binding sites confers a high degree of modulability as required in
most biological interactions, in contrast to the higher stability of a single, strong
bond.
±
21.5
Conclusions
This chapter describes noncovalent, versatile and polyvalent carbohydrate-
carbohydrate interactions in molecular processes. Cell-surface glycoconjugates are
involved in carbohydrate self-interactions in cell recognition processes where
specifi city and fl exibility are essential for proper social behavior of cells. Cell
recognition based on carbohydrate-carbohydrate interactions is unique in that
it displays (i) high variability depending on the degree of molecule clustering
and/or repetition of the binding motif along the carbohydrate chain, and (ii) faster
reactivity than that of protein-protein interactions that typically occur through
integrins, cadherins and other cell adhesion molecules. Therefore, carbohydrate-
carbohydrate interactions are not alternative or supplemental to protein- protein
and protein-carbohydrate interactions. Rather, they represent initial steps leading
to multiple and redundant mechanisms fundamental to cell recognition and
adhesion events. A system, yet to be explored in detail, where carbohydrate-
carbohydrate recognition may play an important role is the binding between
carbohydrate moieties of drugs and the DNA minor groove. Understanding the
molecular basis of this interaction and its importance for the biological activity
of DNA-binding drugs is essential for designing more specifi c and effective
