Hennemann Hanjo, Wirths Sabine, Carl Claudia
Nexigen GmbH, Nattermannallee 1, 50829 Cologne, Germany.
Nexigen GmbH, Nattermannallee 1, 50829 Cologne, Germany.
Eur J Med Chem. 2015 Apr 13;94:489-96. doi: 10.1016/j.ejmech.2014.10.038. Epub 2014 Oct 15.
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.
只有20%-30%的药物靶蛋白能够被常见的药物类型作用，如小分子或治疗性抗体。其余绝大多数蛋白质被认为是“不可成药的”，其中包括在疾病中起重要作用的药物靶蛋白，如转录因子、支架蛋白或衔接蛋白。然而，在过去几年中，包括核苷酸衍生药物（如siRNA、反义核酸）、大环化合物和细胞穿透肽在内的创新化合物类型有了显著发展，现在有潜力调节这些难以作用的靶蛋白以用于治疗。本文将聚焦于细胞穿透肽的发现，并讨论针对肽的细胞内筛选系统，该系统能产生高度相关的肽，因为肽的筛选是在真核细胞中进行的，其条件与后续治疗应用非常相似。
