chapter 2 - Bentham Science

Glycoliposomes and Metallic Glyconanoparticles in Glycoscience Synthesis and Biological Applications of Glycoconjugates 165
Synthetic mimics of the glycocalix, as well as small molecules which intervene in carbohydrate biosynthetic and
processing pathways can be used to interfere with cellular interactions [9]. The design and development of
therapeutic glycomimetics is a great challenge of current glycoscience and the concept of carbohydrate-based drugs
has thus spread out in the last years [10, 11]. The key role of polyvalency in many biological interactions has
suggested new strategies for the design of artificial systems which mimic nature organization and help
understanding cellular events at molecular scale. In particular, different types of scaffolds such as glycopeptides and
glycoproteins [2, 12-14], glycopolymers [15-17], and glycodendrimers [18] have been developed to multimerise
biologically relevant carbohydrates and address biological problems. A big challenge in this direction relies in
combining the effects of multivalency and high local concentrations of the carbohydrates in such systems, with the
possibility of tailoring other types of molecules (vectors, drugs, etc.) on the selected scaffold (multifunctionality)
and/or using different imaging techniques (fluorescence, magnetic resonance imaging [MRI], etc.) to track them in
vitro and in vivo (multimodality). Glycocalixarenes [19] and cyclopeptide-based glycoclusters [20] are presented in
different chapters of this E-book. This chapter is focussed on glycoliposomes and glyconanoparticles (GNPs) as
polyvalent systems for addressing biological problems.
Glycoconjugation and Self-Assembly of Glycoconjugates
The biosynthetic pathways of glycans are lead by enzymatic processes through the action of glycosidases and
glycosyltransferases [21]. Although the isolation from natural sources can give access to biological relevant
oligosaccharides, this method usually affords small amounts of the desired product and rarely provides high degree
of purity. Chemical or chemoenzymatic syntheses still are the method of choice to obtain pure and well-defined
oligosaccharides. The progress in glycoscience is undoubtedly related to the efficiency of routine synthetic methods
of complex glycoconjugates. The developments in the set-up of general methods for the preparation of biologically
relevant oligosaccharides, including multistep protecting-group manipulations and highly stereo- and
chemoselective glycosylations, have recently been reviewed [13, 22, 23]. In addition to traditional solution phase
synthesis, it is nowadays possible to use solid phase synthesis, even in automated fashion [24]. The preparation of
neoglycoconjugates that mimic the functions of bioactive carbohydrates by using chemoselective approaches is of
great importance for the development of new therapeutics and it is revised in two chapters of this E-book [25, 26].
The synthesis of suitable neoglycoconjugates is also essential for the construction of self-assembled glycosystems.
There are two main strategies to construct multivalent carbohydrate-based systems. The first one is to create
membrane-like systems by using carbohydrate-conjugates in the presence of self-assembly molecules, as it is the
case of glycoliposomes (Fig. 1, left), in which a glycolipid is mixed with self-assembly phospholipids and/or
cholesterol(Chol)-like molecules. The other way is to use a suitable scaffold to anchor the carbohydrates, as it is the
case of GNPs (Fig. 1, right), in which a metallic nanocluster is used to covalently attach the glycoconjugates. Due to
the advances in carbohydrates synthesis during the last 30 years, suitable glycoconjugates obtained by conventional
coupling chemistry (amines with carboxy groups or isothiocyanates, thiols with maleimides, azides with alkynes,
etc) have allowed the preparation of a great variety of glycoliposomes and glyconanoparticles. Carbohydrates have
to be derivatised prior to the self-assembly process, although some approaches using unmodified sugars have been
proposed. The main chemical methods used for immobilization and anchoring of oligosaccharides onto solid
matrixes are also valid for surface-functionalization of liposomes and nanoparticles [27].
The self-assembly process of glycolipids in the presence of phospholipids or the self-assembled monolayers (SAMs)
of thiol-armed glycoconjugates are some examples of construction of complex systems in a straightforward way.
Glycoliposomes are non-covalent systems, while glyconanoparticles are based on covalent chemistry. In this
chapter, we review these two types of multivalent systems bio-functionalized with conjugates of biologically
interesting carbohydrates and their application in glycoscience.
GLYCOLIPOSOMES
Amphiphilic phospholipids are able to self-assembly and form closed bilayered structures in water. The resulting
vesicles (liposomes) enclose an aqueous compartment and their structure resembles the phospholipid membranes of
living cells [28]. Liposomes can easily incorporate hydrophilic molecules in their aqueous compartment and