Saccharide-peptide hybrids

We use sugar amino add as a fundional, sucdnct classification term, although a plethora of terms have been proposed in the literature for compounds derived from Saa. These include saccharide-peptide hybrids, glycosamino adds, peptidosaccharides, sac-charopeptides, amide-linked carbohydrates, and carbopeptoids, although the latter compounds most often do not have a peptoid functionality. In some cases Saa are linked to each other, in other cases to amino acids. 

Metzke M, O Connor N, Maiti S et al (2005) Saccharide-peptide hybrid copolymers as biomaterials. Angew Chem Int Ed 44 6529-6533... 

Glycomimetics Linked sugars Spaced sugars Functional mimetics Saccharide-peptide hybrids Sugar amino acids Solid phase synthesis Sialyl Lewis Carbohydrate medicinal chemistry... 

This type of carbohydrate mimetic was coined saccharide-peptide hybrid to point out that carbohydrate properties as well as peptide properties are represented. The mimetics still retain the carbohydrate epitopes available for binding, the p)ranose or furanose ring plus hydroxy groups, as well as the peptide function. 

A number of groups became interested in this class of compounds, and the saccharide-peptide hybrids were coined carbopeptoids [10], glycotides [11], peptidosaccharides [12], or saccharopeptides [13]. In comparison to the formation of oligosaccharides, the complexity in the synthesis of saccharide-peptide hybrids is reduced since no a/ -anomers can be formed. In addition, the oligomerization can be carried out without protecting the hydroxy groups [14] since the amino function is more nucleophilic. We have demonstrated that the oligomerization can also be carried out on a solid phase [14], which opened the way to combinatorial approaches [15,16,17]. 

A mimetic of a (1 2)-linked glycoside was devised by Ichikawa s group [32] using a 3-amino-2,6-anhydro-3-deoxy-heptonic acid building block to arrive at tetramer 23. A two-atom linker replacing the interglycosidic oxygen also characterizes this saccharide-peptide hybrid. A sulfated derivative of 23 blocked syncytium formation caused by HIV infection to CD4 cells at 50 pM concentration. 

Using a C-glycosidic furanoid sugar amino acid, McDevitt and Lansbury [11] prepared a saccharide-peptide hybrid with a three-atom linker, the dimer 26. The homodimer of this C-glycosidic sugar amino acid gave rise to a five-atom spacer as in compound 27 (O Scheme 7) these derivatives have not been reported in deprotected form. 

The term saccharide peptide hybrids (SPHs) encompasses sugar molecules linked by an amide group, e.g. a disaccharide with the interglycosidic oxygen formally replaced by an amide group (Scheme 1). 

The nomenclature of SPHs has not been used consistently. We prefer the term saccharide-peptide hybrids [1] for reasons of clarity. As an abbreviated form, the... 

A first synthesis of a saccharide-peptide hybrid in a directed synthesis was performed by Yoshimura et al. in 1976 [50], The CAA 51 was activated with cyclo-hexylcarbodiimide and linked to amino sugar 52 to result in dimer 53. This glucuronic acid amide was less soluble in water than the corresponding mannuronic acid derivative. Dimer 53 could be converted, after removal of the anomeric protecting group by hydrogenation, to the amide-linked alditol 54 (Scheme 8) by reduction with sodium borohydride. This publication was not followed up at the time until the interest in carbohydrate mimetics rose [51]. 

---