Abstract
The development of complex molecular scaffolds with defined folding properties represents
a central challenge in chemical research. Proteins are natural scaffolds defined by
a hierarchy of structural complexity and have evolved to manifest unique functional
characteristics; for example, molecular recognition capabilities that facilitate the
binding of target molecules with high affinity and selectivity. Utilizing these features,
proteins have been used as a starting point for the design of synthetic foldamers
and enhanced biocatalysts, as well as bioactive reagents in drug discovery. In this
account, we describe the strategies used in our group to stabilize protein folds,
ranging from the constraint of bioactive peptide conformations to chemical protein
engineering. We discuss the evolution of peptides into peptidomimetics to inhibit
protein–protein and protein–nucleic acid interactions, and the selective chemical
modification of proteins to enhance their properties for biotechnological applications.
The reported peptide- and proteomimetic structures cover a broad range of molecular
sizes and they highlight the importance of structure stabilization for the design
of functional biomimetics.
1 Introduction
2 Constraining the Conformation of Peptides
3 Peptide-Based Covalent Protein Modifiers
4 Chemical Protein Engineering
5 Conclusions
Key words
INCYPRO - peptidomimetics - protein engineering - protein–protein interactions - proteomimetics
- structure-based design
