Sugar-peptide hybrids

The presence of amino and carboxylic acid groups conveniently protected allows for the coupling of the SAAs building blocks to form sugar-peptide hybrids. One or more amino acids of the peptidic backbone can be replaced by the sugar units, thus incorporating the conformation-... 

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. 

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

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). 

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]. 

The so-called peptide nucleic acids (PNAs) 2.67 (140-142) are examples of the replacement of the entire sugar-phosphate backbone with different functionah-ties that retain biological activity. The chemistry is similar to SP peptide synthesis employing Boc or Fmoc protocols (see Section 2.1). Peptide-ON hybrids, where either one (143) or two (144) of the ON termini are attached to peptide chains, have been reported. Acyclic silicon phosphoramidites 2.68 (145) have also been used for SPS of silicon-containing ON analogues. 

More often the click reaction is used in the modification of biopolymers. An example is sugar-derived imaging in live animals. Glycans in live zebrafish embryos light up when the embryos are fed azide-derived sugars and are subsequently treated with difluori-nated cyclooctyne derived probes. Elastin-like hybrid polymers, based on the reaction of azide-terminated poly (ethylene oxide) (PEG) and alkyne functionalized peptides, are also developed. These polymers are intended to grow new vocal cords . 

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