Sialic acids are a diverse family of naturally occurring 2-keto-3-deoxy-nononic acids, amongst which N-acetylneuraminic acid (Neu5Ac) is the most common, that are involved in a wide range of biological processes.
Sialic acids
normally appear at terminal positions of oligosaccharides of
glycoproteins and glycolipids where they are a(2,3) or a(2,6) linked to
galactosides or
a(2,6) linked to 2-acetamido-galactosides. The
disialosyl structures Neu5Aca(2-8)Neu5Ac and Neu5Aca(2-9)Neu5Ac have
also been found as constituents of oligosaccharides of glycoproteins
and lipids.
As components of
sugar-protein and sugar-lipid compounds (glycoconjugates), sialic acids
cover all cells of higher animals and man with an negatively charged
coat and exert a variety of different biological functions. In fact, in
this exposed position sialic acids are important regulators of cellular
and molecular interactions, where they can either act as recognition
determinants or masking agents. For the latter, sialic acid 'masks' the
oligosaccharide chain by the action of hormone receptors or antigens.
As recognition determinant sialic acids modulate cell growth,
differentiation and cell adhesion. Another interesting aspect of the
biological proprieties of sialic acid is its involvement in certain
diseases: sialic acid-specific adhesion of bacteria and viruses is a
phenomenon drawing an increasing level of interest, as a critical step
in infectious diseases. It has been known for many years that microbial
pathogens, i.e., viruses, mycoplasma, bacteria, and protozoa, take
advantage of cell surface sialic acids to adhere to their respective
host cell. In addition, sialo-conjugates have been related to diseases
such as atherosclerosis, asthma as well as oncogenesis.
Although extensively explored, the chemical
synthesis of sialosides in high yield and stereoselectivity is still a
challenge.
In our group we are investigating new
methodologies for the stereocontrolled synthesis of a sialosides,
studying different novel leaving groups as well as
conformationally modified sialyl donors and acceptors.