Poster Presentation 14th Australian Peptide Conference 2022

Developing Transmembrane Ion Channel Using α-Peptide-Oligourea Chimera: Dissecting Ion Selectivity and Pathway (#404)

CHIRANJIT Dr DUTTA 1 2 , Pannaga Dr Krishnamurthy 1 2 , Sung Hyun Dr Yoo 3 , Morgane Dr Pasco 3 , Gilles Prof Guichard 3 , Manjunatha Prof Kini 2 , Prakash Prof Kumar 1 2
  1. NUS Environmental Research Institute (NERI), National University of Singapore, singapore, Singapore
  2. National University of Singapore, Singapore, SINGAPORE
  3. Université de Bordeaux, CBMN, UMR 5248, Institut Européen de Chimie et Biologie, 2 rue Robert Escarpit, Pessac, Pessac, 33607, France

Abstract

Constructing artificial transmembrane ion channel is a challenging yet rewarding task1,2. We describe here a de novo design of transmembrane ion channels made up of peptide-oligourea chimera3,4. A short peptide chain was connected to oligourea segment to create peptide-oligourea chimera with diversity and tunability in the sequence4. Native mass spectrometry and TEM analyses showed that these chimeras in aqueous solution form oligomeric structures along with fiber bundle networks akin to biomolecules3,4. This encouraged us to investigate their functionality. Fluorescence-based assay demonstrated that the ion transport activity across lipid bilayer was facilitated by chimeras with anion selectivity that occurs by X-/OH- (X-=Cl-, Br-, I-, F-) antiport mechanism assigned by FCCP and valinomycin cotransport assay5,6. Fractional activity (Y) of chimeras revealed that anion selectivity follows the halide ion topology of Cl->Br->I->F-. However, poor transport of weakly basic anions (OAc-, F-) indicates that the anion selectivity through these channels depends mainly on energetic factors rather than the size exclusion effects (OAc->>F-)5,6. Overall, this study shows that peptide-oligourea based de novo design can yield unique bio-active molecules with well predicted structure and function.

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