Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstraße 2, 37077, Göttingen, Germany.
Abteilung für Neurobiologie, Max-Planck-Institut für Biophysikalische Chemie, Am Fassberg 11, 37077, Göttingen, Germany.
Angew Chem Int Ed Engl. 2018 Nov 5;57(45):14932-14936. doi: 10.1002/anie.201805752. Epub 2018 Oct 9.
Membrane fusion is an essential process in nature and is often accomplished by the specific interaction of SNARE proteins. SNARE model systems, in which SNARE domains are replaced by small artificial units, represent valuable tools to study membrane fusion in vitro. The synthesis and analysis is presented of SNARE model peptides that exhibit a recognition motif composed of two different types of peptide nucleic acid (PNA) sequences. This novel recognition unit is designed to mimic the SNARE zippering mechanism that initiates SNARE-mediated fusion. It contains N-(2-aminoethyl)glycine-PNA (aeg-PNA) and alanyl-PNA, which both recognize the respective complementary strand but differ in duplex topology and duplex formation kinetics. The duplex formation of PNA hybrid oligomers as well as the fusogenicity of the model peptides in lipid-mixing assays were characterized and the peptides were found to induce liposome fusion. As an unexpected discovery, peptides with a recognition unit containing only five aeg-PNA nucleo amino acids were sufficient and most efficient to induce liposome fusion.
膜融合是自然界中一种基本的过程，通常是通过 SNARE 蛋白的特异性相互作用来完成的。SNARE 模型系统中，SNARE 结构域被小的人工单元取代，是研究体外膜融合的有价值的工具。本文介绍了 SNARE 模型肽的合成和分析，这些模型肽具有由两种不同类型的肽核酸（PNA）序列组成的识别基序。这种新的识别单元旨在模拟引发 SNARE 介导融合的 SNARE 拉链机制。它包含 N-(2-氨乙基)甘氨酸-PNA(aeg-PNA)和丙氨酰-PNA，两者都识别各自的互补链，但在双链拓扑和双链形成动力学上有所不同。PNA 杂交寡聚物的双链形成以及模型肽在脂质混合测定中的融合性被表征，发现这些肽诱导了脂质体融合。令人意外的是，仅含有五个 aeg-PNA 核碱基的识别单元的肽足以且最有效地诱导脂质体融合。
