Preparation and conformational analysis of polyproline tri-helix macrocycle nanoscaffolds of varied sizes
Journal
Nanoscale
Journal Volume
13
Journal Issue
8
Pages
4592-4601
Date Issued
2021
Author(s)
Abstract
Ligand patterns at the nanoscale are essential in modulating biological recognition and signaling through binding to receptor oligomers. Biocompatible nanoscaffolds that allow precise control of multiple ligand presentation would be of great use in manipulating cellular processes and understanding membrane receptor biology. We have previously developed tri-helix and tetra-helix macrocycle scaffolds based on the Pro9 peptide helix to control ligand arrangements that can selectively target receptor oligomers. A better understanding of the structure of these macromolecules would significantly reduce the difficulty in designing matching ligand positions for target receptors. In this work, we expand the arsenal of ligand patterns by preparing polyproline tri-helix macrocycle scaffolds of different sizes. These synthetic nanoscaffolds composed of peptide helices ranging from Pro6 to Pro12 also allowed us to systematically investigate their properties. With a combination of circular dichroism spectroscopy and ion mobility spectrometry-mass spectrometry (IMS-MS), the measurement for varied sizes of these scaffolds indicated the connecting dihedral angle between both ends of the helix affects the strain in the cyclic scaffold. The experimental collision cross section obtained from IMS-MS favors a propeller model for the helix arrangements. The results not only contribute conformational insights for the polyproline tri-helix system, but also provide precious information for the future design and synthesis of cyclic nanostructures based on peptide helices. ? 2021 The Royal Society of Chemistry.
Subjects
Biocompatibility; Circular dichroism spectroscopy; Dichroism; Dihedral angle; Ion mobility spectrometers; Mass spectrometry; Oligomers; Peptides; Biological recognition; Cellular process; Collision cross sections; Conformational analysis; Ion mobility spectrometry; Membrane receptors; Multiple ligands; Precise control; Ligands; ligand; peptide; polyproline; circular dichroism; conformation; mass spectrometry; Circular Dichroism; Ligands; Mass Spectrometry; Molecular Conformation; Peptides
Type
journal article