Carbohydrates in Peptide and Protein Design - Peptide and Protein Design for Biopharmaceutical Applications - page 196

5.8 CARBOPROTEINS: PROTEIN MODELS ON

CARBOHYDRATE TEMPLATES

'Carbopeptides' and 'carboproteins' (for a review, see [90]) are peptide
and protein chimeras assembled on a carbohydrate template, inspired by
Mutter's concept of TASPs [91]. Monosaccharides were utilized as tem-
plates due to their polyfunctionality, the relative rigidity of their pyranose
ring forms and their ease of access to epimers. Furthermore, a vast
literature describes the regiospecific manipulation of their functional
groups. Using the primary and secondary hydroxyls of mono- or disac-
charides should provide flexible control of the directionality and dis-
tances between anchoring points for peptide chains in the de novo
design of protein models.
Carboproteins have been designed to mimic a-helix bundles [92].
A convergent modular synthesis strategy was adopted in which peptide
aldehydes were coupled to the carbohydrate template by oxime ligation
[93-97]. This provided carboproteins on Gal p , Glc p and Alt p templates
(Figure 5.15) [95,96]. Biophysical studies with CD and H-D exchange
NMR spectroscopy clearly indicated formation of a-helix bundles.

P
e
p
t
i
d
e

P
e
p
t
i
d
e

P
e
p
t
i
d
e

RO

′

RO

′

O

NH

R ′ O

HN

RO OR

′

P
e
p
t
i
d
e

N

Alt p

N

O NH

O

OR

′

O O - N

O O

O O

O

O

R ′ O

R ′ O

HN O

R O

′

O

OR

OR

Glc p

N O O

Figure 5.15 Left: a carboprotein prepared by chemoselective oxime ligation on an
aminooxy acetyl functionalized Gal p template. R: OCH 3 or C 6 H 4 -NHCO-
CH 2 SH; peptide: Ac-EALEKALKEALAKLG- or Ac-YEELLKKLEELLKKA-. Right:
Glc p and Alt p templates; R: peptide with C-terminal linker [95-97]