Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cells. 2021 Mar 8;10(3):597. doi: 10.3390/cells10030597.
Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.
自 20 世纪 20 年代胰岛素治疗糖尿病患者取得开创性突破以来，人们一直热衷于开发其他蛋白质及其肽模拟物，将其作为治疗各种其他医学疾病的疗法。目前，至少有 60 种不同的肽已被批准用于人体，还有 150 多种肽处于不同的临床开发阶段。针对脂蛋白上的主要蛋白质（即载脂蛋白）的肽模拟物最初也被开发为了解载脂蛋白结构的工具，最近也被开发为潜在的治疗方法。在这篇综述中，我们讨论了基于载脂蛋白 AI、载脂蛋白 E 和载脂蛋白 C-II 的肽的生物化学、肽模拟物设计和临床试验。我们主要关注与心血管疾病相关的肽模拟物的应用。最后，我们讨论了肽作为治疗剂的局限性，以及在将载脂蛋白模拟肽开发成新药之前需要克服的挑战。
