Synthesis and Investigation of Nucleobase Functionalized β-Peptide as SNAREs Model System for Membranefusion

by Muheeb Sadek
Doctoral thesis
Date of Examination:2015-05-26
Date of issue:2015-07-22
Advisor:Prof. Dr. Ulf Diederichsen
Referee:Prof. Dr. Claudia Steinem
Referee:Prof. Dr. Reinhard Jahn
Persistent Address: http://dx.doi.org/10.53846/goediss-5194

 

 

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Abstract

English

In this work, the novel simplified SNARE-mimicking systems consisting of TMD/linker segments of the natural membrane-bound SNARE proteins (syntaxin-1A and synaptobrevin 2) with a nucleobase functionalized β-peptide (β-PNA) recognition motif were designed and synthesized. The β-PNAs allow antiparallel orientation and therefore, a fusion mechanism is addressed, that differs from the native SNARE situation. Nevertheless, the artificial TMD/linker/β-PNA constructs are surprisingly efficient in mediating membrane fusion. The β-PNA recognition motif with the linear and conformational rigid 14-helix backbone offers an especially interesting option of distance control between the vesicles. This system offers a powerful tool to control the fusion state by using different length of β-PNA. The extended β-PNA leads to hemifusion state while the shortened one induces full fusion.
Keywords: SNARE protein; Fusion distance controlling; Parallel fusion system; Nucleobase functionalized β-peptide
 
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