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PNA Hybrid Sequences as Recognition Units in SNARE‐Protein‐Mimicking Peptides
Author(s) -
Hubrich Barbara E.,
Kumar Pawan,
Neitz Hermann,
Grunwald Matthias,
Grothe Tobias,
Walla Peter Jomo,
Jahn Reinhard,
Diederichsen Ulf
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201805752
Subject(s) - computational biology , chemistry , computer science , pattern recognition (psychology) , biology , artificial intelligence
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.