Chemistry Reference
In-Depth Information
4
The Chemist's Way to Prepare Multivalency
Yoann M. Chabre and Ren é Roy
Carbohydrates have distinct characteristics to enable high-density coding, among
which positional branching constitutes unique features (see Summary Box of
Chapter 1). The branching generates multivalency. The valency of molecular struc-
tures bearing carbohydrate ligands at the periphery is defi ned as the number of
identical units that can each contribute to binding contacts with suitable receptors
(for example lectins) [1]. Thus, a glycoconjugate that has two copies of a binding
carbohydrate moiety is said to be divalent. Similarly, multivalent interactions are
defi ned as specifi c associations of multiple carbohydrate ligands present on a
molecular surface that bind multiple receptors expressed on proteins or cell sur-
faces. The importance of these multivalent carbohydrate- protein interactions is
critical to several biological phenomena discussed throughout this topic. In fact,
mammals only express nine different carbohydrates that are arranged in variable
linkages (the ' sugar coding ' ) (please see Figure 1.6 for monosaccharide structures
and Chapter 3 for synthetic aspects leading to branched oligosaccharides). This
family of natural as well as synthetic species has been designed to compensate for
the usually low binding affi nity (
K
a
) of carbohydrate ligands (for further details,
please see Chapter 13). The main goal of this chapter is to highlight synthetic
strategies that have been created to enhance carbohydrate- protein interactions at
the molecular level by architectures resembling ' carbohydrate Velcro ' . [Velcro,
used to attach shoelaces, is made of several tiny hooks and loops each forming
weak bindings. It was invented by a Swiss engineer George de Mistral in 1945
after his close observation of burdock (
Arctium lappa
, Figure 4.1c) sticking to his
clothes during his daily summer walks in the Alps. The word velcro is derived
from the French '
vel ours
' (velvet) and '
cro chet
' (hook)]. These novel structures are
assembled by strategies analogous to the constructions of ' Lego toys ' . Chemists
are therefore playing essential roles in modern glycobiology.
Nature's multivalency is often expressed by 'dendritic' architectures that repre-
sent the most pervasive topologies observed in plant and animal kingdoms.
Numerous examples of these patterns may be found at different dimensional
length scales (meters to microns) and typical examples can be observed in abiotic
systems (for example snow crystals, fractal erosions, manganese dendrites on
