Department of Chemistry and the Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, United States.
Biochim Biophys Acta Proteins Proteom. 2021 Jan;1869(1):140553. doi: 10.1016/j.bbapap.2020.140553. Epub 2020 Sep 28.
The discovery of enzyme-derived d-amino acid-containing peptides (DAACPs) that have physiological importance in the metazoan challenges previous assumptions about the homochirality of animal proteins while simultaneously revealing new analytical challenges in the structural and functional characterization of peptides. Most known DAACPs have been identified though laborious activity-guided purification studies or by homology to previously identified DAACPs. Peptide characterization experiments are increasingly dominated by high throughput mass spectrometry-based peptidomics, with stereochemistry rarely considered due to the technical challenges of identifying l/d isomerization. This review discusses the prevalence of enzyme-derived DAACPs among animals and the physiological consequences of peptide isomerization. Also highlighted are the analytical methods that have been applied for structural characterization/discovery of DAACPs, including results of several recent studies using non-targeted discovery methods for revealing novel DAACPs, strongly suggesting that more DAACPs remain to be uncovered.
酶衍生的含有 D-氨基酸的肽（DAACPs）的发现，对后生动物中蛋白质的手性均一性提出了挑战，同时也揭示了在肽的结构和功能表征方面的新的分析挑战。大多数已知的 DAACPs 是通过艰苦的基于活性的纯化研究或与先前鉴定的 DAACPs 的同源性来鉴定的。肽特征实验越来越多地由基于高通量质谱的肽组学主导，由于确定 l/d 异构化的技术挑战，立体化学很少被考虑。本文讨论了酶衍生的 DAACPs 在动物中的普遍性以及肽异构化的生理后果。还强调了已应用于 DAACP 结构表征/发现的分析方法，包括使用非靶向发现方法揭示新的 DAACPs 的几项最新研究的结果，这强烈表明还有更多的 DAACPs 有待发现。
