Watt Paul M, Milech Nadia, Stone Shane R
Phylogica Ltd., 100 Roberts Road, Subiaco 6008, Western Australia, Australia; Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Subiaco 6008, Western Australia, Australia.
Phylogica Ltd., 100 Roberts Road, Subiaco 6008, Western Australia, Australia; Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Subiaco 6008, Western Australia, Australia.
Curr Opin Chem Biol. 2017 Jun;38:127-133. doi: 10.1016/j.cbpa.2017.03.016. Epub 2017 May 18.
Phylomers are peptides derived from biodiverse protein fragments. Genetically encoded Phylomer libraries have been constructed, containing hundreds of billions of peptides derived from virtually all of the few thousand fold families found in the protein universe. They offer a rich source of high quality hits against diverse target sequences and have been used for three main purposes: firstly, to identify and validate targets in phenotypic screens; secondly, to block protein interactions with nanomolar potency binding affinities; thirdly as a source of more efficient cell penetrating peptides for the delivery of a wide range of biologics. Phylomer libraries are being increasingly used in applications such as phenotypic screening where the numbers of peptides which can be feasibly screened is limited. Phylomers also offer access to the intracellular target landscape, which remains largely undruggable by conventional means.
系统进化肽是源自生物多样性蛋白质片段的肽。已经构建了基因编码的系统进化肽文库，其中包含数千亿个肽，这些肽几乎来自蛋白质宇宙中发现的数千个折叠家族中的所有家族。它们为针对不同靶序列提供了丰富的高质量命中物来源，并已用于三个主要目的：第一，在表型筛选中识别和验证靶标；第二，以纳摩尔效力的结合亲和力阻断蛋白质相互作用；第三，作为更有效的细胞穿透肽的来源，用于递送多种生物制剂。系统进化肽文库越来越多地用于诸如表型筛选等应用中，在这些应用中，可实际筛选的肽数量有限。系统进化肽还提供了进入细胞内靶标领域的途径，而传统方法在很大程度上仍无法作用于该领域。
