chapter 2 - Bentham Science

164 Synthesis and Biological Applications of Glycoconjugates, 2011, 164-202
Glycoliposomes and Metallic Glyconanoparticles in Glycoscience
Marco Marradi a,b,* , Fabrizio Chiodo a , Isabel García a,b and Soledad Penadés a,b
Olivier Renaudet and Nicolas Spinelli (Eds)
All rights reserved - © 2011 Bentham Science Publishers
CHAPTER 10
a Laboratory of GlycoNanotechnology, Biofunctional Nanomaterials Unit, CIC biomaGUNE, Parque Tecnológico de
San Sebastián, Pº de Miramón 182, 20009 San Sebastián, Spain and b Biomedical Research Networking Center in
Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Parque Tecnológico de San Sebastián, Pº de
Miramón 182, 20009 San Sebastián, Spain
Abstract: Multivalent sugar-based materials have attracted attention since the functional role of carbohydrates in
biology has been disclosed. The design of artificial systems that mimics the polyvalent carbohydrate organization
at cell surface has been envisaged as a strategy to study and intervene in carbohydrate-mediated interactions. One
of the first synthetic glycomaterials which appeared in the literature were glycoliposomes, dynamic systems that
resemble the glycocalix in the phospholipidic bilayer of cell membranes. Glycoliposomes are non-covalent
systems which have been used since the seventies as multivalent tools in carbohydrate-based interactions against
pathogens, for enhancing immunity and as molecular carriers in drug delivery. In former years, the advent of
nanotechnology has allowed the design and construction of new materials similar in size to biologically relevant
molecules (proteins, nucleic acids, etc) and displaying unique physical properties. The bio-functionalization of
metallic nanomaterials with carbohydrates generated a new class of glycomaterials, named glyconanoparticles,
which present carbohydrates in a highly multivalent way and in high local concentrations. At the same time, the
quantum size properties of metallic nanoclusters can be used for biosensing, diagnostics, and (in perspective)
therapy. This review focuses on glycoliposomes and covalently-functionalized glyconanoparticles which make
use of the “glyco-code” to address specifically pathogens or pathological-related problems.
Keywords: Glycoliposomes, glyconanoparticles, glycocalix, multivalency, neoglycolipids.
INTRODUCTION
The Functional Role of Carbohydrates
Once thought to be only energetic sources for living systems or structural molecules protecting the cell surface,
carbohydrates are nowadays recognized as essential tools for cell adhesion and recognition processes [1]. The surface of
mammalian cells is covered by a dense coating of carbohydrates named glycocalyx. In the glycocalyx, carbohydrates
appear mainly conjugated to proteins and lipids (glycoproteins, glycolipids and proteoglycans) and it is as clustered
glycoconjugates that they develop their biological function. The high variety of carbohydrates, which have a much
higher information store-capacity than amino acids and nucleotides, gives rise to a complex “glycocode” which is used
by living systems to stock and transmit biological information. The (oligo)saccharides of the glycocalix are involved in
carbohydrate-protein [2] and carbohydrate-carbohydrate [3] interactions that mediate many physiological and
pathological processes [4, 5]. Carbohydrate-mediated interactions are generally very weak and the low affinity has to be
compensated by multivalent presentation of the ligands. Polyvalent ligand–receptor interactions are characterized by the
simultaneous binding of multiple ligands on one biological entity to multiple receptors on another biological entity and
can be cooperatively much stronger than corresponding monovalent interactions [6]. These interactions are ubiquitous in
biology and include both cellular signalling and matching contacts of viral and bacterial surfaces to host cells. For
example, the weak association constant of carbohydrate-protein interactions in living systems is overcome both by
clustering of sugar binding sites in the protein partner and presenting the carbohydrate at cell surface in a multivalent and
orientated way [2, 7]. The structural diversity, the variability of sugar–units sequence and linkage points, the anomeric
configuration, the chemical modification and/or substitution at different positions and with different groups (phosphate,
sulphate, N-acetyl, etc), and the interconversion of conformers are some characteristics that create a unique level of
diversity in the “glycocode”. Another key feature of the “glycocode” relies on the potential of glycoconjugates to adopt
various defined shapes, each with its own particular ligand properties (differential conformer selection) [8].
*Address correspondence to Marco Marradi: Laboratory of GlycoNanotechnology, Biofunctional Nanomaterials Unit, CIC biomaGUNE,
Parque Tecnológico de San Sebastián, Pº de Miramón 182, 20009 San Sebastián, Spain: E-mail: mmarradi.ciber-bbn@cicbiomagune.es