Carbohydrates in Peptide and Protein Design - Peptide and Protein Design for Biopharmaceutical Applications - page 185

5.6 SUGAR AMINO ACIDS

A sugar (carbohydrate) amino acid (SAA) is a compound with immediate
linkages of both amino and carboxy functionalities to a carbohydrate
frame [34]. SAAs can be found widely distributed in nature, with sialic
acid being the most prominent example (Figure 5.5). Sialic acid is the
name for both the family of N- and O-acyl derivatives of neuraminic acid
that are found peripherally on glycoproteins and for the most common
member of this group, Neu5Ac.

Figure 5.5 The naturally-occurring sugar (carbohydrate) amino acid (SAA) neuraminic
acid

Synthetic SAAs can be prepared from commercially available mono-
saccharides. The amino functionality can be introduced as an azide,
cyanide or nitromethane equivalent, followed by subsequent reduction.
Likewise, the carboxylic acid moiety can be introduced directly with
CO 2 , by reduction of a cyanide, by oxidation of an olefin or via selective
oxidation of a primary alcohol. The latter method was used by Heyns and
Paulsen in 1955 for the first synthesis of an SAA, glucosaminuronic acid,
by oxidation of glucosamine [35]. Since then, SAAs have been synthesized
by Kessler [34], Fleet, Le Merrer, Chakraborty [36,37], Dondoni [38] and
many others, and include b-, g- and d-SAAs, as well as both furanoside
and pyranoside ring forms (Figure 5.6). Also, sugar mimetics in which the

Carbohydrate

O

H 2 N COOH

n

H 2 N COOH

n n

R

O

R

O

O

R

H 2 N COOH H 2 N COOH H 2 N COOH

n n

n n n n

Figure 5.6 Schematical presentation of five classes of SAA: a-amino acids, epoxides,
oxetanes, furanosides and pyranosides. Inspired by Ref. 39