title: Cell-based peptide screening to access the undruggable target space.
abstract: Only 20-30% of drug target proteins can be accessed by common drug classes, like small molecules or therapeutic antibodies. The vast majority of the remaining proteins are considered "undruggable" and include drug target proteins, like transcription factors, scaffold or adapter proteins, which play important roles in disease. However over the last years innovative compound classes including nucleotide derived drugs (e.g. siRNA, antisense), macrocyclic compounds and cell-permeable peptides matured significantly and hold now the potential to modulate these hard to access target proteins for therapeutic use. This article will focus on the discovery of cell-permeable peptides and discuss intracellular screening systems for peptides, which yield highly relevant peptides, because peptide selection takes place in eukaryotic cells, under conditions, which are very similar to the later therapeutic use.
authors.affiliation: Nexigen GmbH, Nattermannallee 1, 50829 Cologne, Germany. Electronic address: hahenn@gmx.net.
authors.forename: Hanjo
authors.initials: H
authors.lastname: Hennemann
authors.affiliation: Nexigen GmbH, Nattermannallee 1, 50829 Cologne, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wirths
authors.affiliation: Nexigen GmbH, Nattermannallee 1, 50829 Cologne, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carl
mesh_terms: D057846:Cell-Penetrating Peptides / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D002477:Cells / Q000187:drug effects / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019151:Peptide Library; D011506:Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D057846:Cell-Penetrating Peptides; D019151:Peptide Library; D011506:Proteins
keywords: Cell-permeable peptides; Drug; Drug discovery; Library; Peptide screening; Screening; Therapeutics; Undruggable targets