Chemistry Reference
In-Depth Information
15
PEPTIDE DENDRIMERS AS
ARTIFICIAL PROTEINS
T
AMIS
D
ARBRE AND
J
EAN
-L
OUIS
R
EYMOND
Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3,
CH-3012, Berne, Switzerland
15.1 INTRODUCTION
Dendrimers have been suggested early on as synthetic macromolecular analogs of
proteins [1-4], in particular enzymes [5,6]. Indeed the tree-like dendrimer topology
produces macromolecules that are expected to adopt a protein-like globular
structure without the need for folding, thus circumventing an important obstacle
in artificial protein design [7]. Most synthetic work with dendrimers has however
remained quite distant from proteins for two reasons: (1) the building blocks used
for dendrimers are quite different from the proteinogenic
-amino acids; (2) the use
of fixed branching structures with changes possible only at the dendrimer core or at
the periphery strongly limits structural variations compared to natural proteins
where changes occur by amino acid substitution throughout the structure. For
instance in early work by Denkewalter and coworkers with poly-lysine dendri-
mers [8] and in the multiple antigenic peptides by Tam and coworkers [9], a poly-
lysine tree is used for the only purpose of providing multivalency without reference
to artificial protein design.
In this chapter, we review our approach to peptide dendrimers as artificial
proteins [10]. The work is based on the combinatorial solid-phase synthesis of
peptide sequences featuring diamino acids branching points at every 2
nd
,3
rd
,or
4
th
position to obtain peptide dendrimers that can be easily varied at the core, within
a
