Carbohydrates in Peptide and Protein Design - Peptide and Protein Design for Biopharmaceutical Applications - page 197

Surprisingly, a carboprotein assembled on an Alt p template showed a
higher content of a-helix than similar carboproteins prepared on Gal p
and Glc p [96]. This indicated that the template has a controlling effect on
the a-helix bundle structure. However, small-angle X-ray scattering
(SAXS) indicated that a 3 þ 1-helix structure had formed, instead of the
expected 4-helix bundle [94]. Carboproteins are described in greater
detail in Chapter 6.

5.9 CONCLUSION

The hydrophilicity of carbohydrates has been employed in the
design of neoglycopeptides with improved physical and biochemical
properties compared to the unmodified peptides. The great potential
of carbohydrates as scaffolds in peptide redesign is based on their
structural features, including furanoid vs. pyranoid ring forms, axial
vs. equatorial orientation of hydroxyls, relatively rigid pyranoside
ring forms, regioisomeric hydroxyls, introduction of amino and car-
boxyl groups, and monosaccharide vs. oligosaccharide (e.g. cyclodex-
trin) structures. This potential has been converted into successful
applications of carbohydrates in the de novo design of glyco-
peptides, peptidomimetics, proteinmimetics and cyclodextrin-peptide
conjugates.
Carbohydrate derivatives, for example SAAs, have proven especially
valuable in the design of turn mimetics, as furanosides and pyranosides
can display substituents with an equatorial orientation. Monosaccharides
have also been used quite successfully as central, organizing scaffolds in
mimetics of cyclic peptides and for template-assembled proteinmimetics.
For the most part, two properties of cyclodextrins have been utilized: the
well-defined distances between different 6-OHs and the hydrophobicity
of the cavity.
Still, only a limited selection of carbohydrates has been used so far;
for example, the axial vs. equatorial orientation of hydroxyls has not
been fully exploited for display of ligands. The configurational and
conformational properties of carbohydrates have to be balanced with
appropriate spacers from the carbohydrate ring substituents. Too-long
spacers are likely to abolish the chiral information in the carbohydrate
moiety. There are only a few examples of a direct effect from the
stereochemical nature of a carbohydrate template, one being Alt p vs.
Glc p carboproteins [96].