title: Encoded libraries of chemically modified peptides.
abstract: The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Although encoded peptide libraries are typically several orders of magnitude larger than classical chemical libraries, can be more readily screened, and can give rise to higher affinity ligands, their use as pharmaceutical ligands is limited by their intrinsic properties. Two of the intrinsic limitations include the rotational flexibility of the peptide backbone and the limited number (20) of natural amino acids. However these limitations can be overcome by use of chemical modification. For example, the libraries can be modified to introduce topological constraints such as cyclization linkers, or to introduce new chemical entities such as small molecule ligands, fluorophores and photo-switchable compounds. This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries.
authors.affiliation: Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland. Electronic address: christian.heinis@epfl.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Heinis
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom. Electronic address: winter@mrc-lmb.cam.ac.uk.
authors.forename: Greg
authors.initials: G
authors.lastname: Winter
mesh_terms: D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D055808:Drug Discovery; D015870:Gene Expression; D015723:Gene Library; D006801:Humans; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000737:chemistry*; D057786:Peptidomimetics / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D019151:Peptide Library; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D054852:Small Molecule Libraries; D004247:DNA