The design, structures and therapeutic potential of protein epitope mimetics.
Using a biologically relevant peptide or protein structure as a starting point for lead identification represents one of the most powerful approaches in modern drug discovery. Here, we focus on the protein epitope mimetic (PEM) approach, where folded 3D structures of peptides and proteins are taken as starting points for the design of synthetic molecules that mimic key epitopes involved in protein-protein and protein-nucleic acid interactions. By transferring the epitope from a recombinant to a synthetic scaffold that can be produced by parallel combinatorial methods, it is possible to optimize target affinity and specificity as well as other drug-like ADMET properties. The PEM technology is a powerful tool for target validation, and for the development of novel PEM-based drugs.
Robinson
John A
JA
Organic Chemistry Institute, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Demarco
Steve
S
Gombert
Frank
F
Moehle
Kerstin
K
Obrecht
Daniel
D
D000818:Animals; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D018716:Molecular Mimicry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*
D000939:Epitopes; D011506:Proteins