The Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.
Biopolymers. 2011;96(5):545-55. doi: 10.1002/bip.21573.
Peptoid oligomers were initially developed as part of a larger basic research effort to accelerate the drug-discovery process in the biotech/biopharma industry. Their ease of synthesis, stability, and structural similarity to polypeptides made them ideal candidates for the combinatorial discovery of novel peptidomimetic drug candidates. Diverse libraries of short peptoid oligomers provided one of the first demonstrations in the mid-1990s that high-affinity ligands to pharmaceutically relevant receptors could be discovered from combinatorial libraries of synthetic compounds. The solid-phase submonomer method of peptoid synthesis was so efficient and general that it soon became possible to explore the properties of longer polypeptoid chains in a variety of areas beyond drug discovery (e.g., diagnostics, drug delivery, and materials science). Exploration into protein-mimetic materials soon followed, with the fundamental goal of folding a non-natural sequence-specific heteropolymer into defined secondary or tertiary structures. This effort first yielded the peptoid helix and much later the peptoid sheet, both of which are secondary-structure mimetics that are close relatives to their natural counterparts. These crucial discoveries have brought us closer to building proteinlike structure and function from a non-natural polymer and have provided great insight into the rules governing polymer and protein folding. The accessibility of peptoid synthesis to chemists and nonchemists alike, along with a lack of information-rich non-natural polymers available to study, has led to a rapid growth in the field of peptoid science by many new investigators. This work provides an overview of the initial discovery and early developments in the peptoid field.
肽缩氨酸齐聚物最初是作为生物技术/制药行业药物发现过程加速的基础研究的一部分而开发的。它们易于合成、稳定，且结构与多肽相似，使它们成为新型肽模拟药物候选物组合发现的理想候选物。短肽缩氨酸齐聚物的多样化文库在 20 世纪 90 年代中期首次证明，从合成化合物的组合文库中可以发现对药物相关受体具有高亲和力的配体。肽缩氨酸合成的固相亚单体方法非常高效和通用，因此很快就可以在药物发现以外的各种领域（例如诊断、药物输送和材料科学）探索长肽缩氨酸链的性质。对蛋白质模拟材料的探索紧随其后，其基本目标是将非天然序列特异性杂聚物折叠成定义的二级或三级结构。这项工作首先产生了肽螺旋，后来又产生了肽片，它们都是二级结构模拟物，与天然结构非常相似。这些关键发现使我们更接近于从非天然聚合物构建类似蛋白质的结构和功能，并为聚合物和蛋白质折叠的规律提供了深刻的见解。肽缩氨酸合成对化学家以及非化学家的易用性，以及缺乏可供研究的信息丰富的非天然聚合物，导致许多新的研究人员在肽缩氨酸科学领域迅速发展。这项工作概述了肽缩氨酸领域的最初发现和早期发展。
