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Peptoid Residues Make Diverse, Hyperstable Collagen Triple Helices

preprint
submitted on 05.09.2020 and posted on 08.09.2020 by Julian Kessler, Grace Kang, Zhao Qin, Helen Kang, Frank Whitby, Thomas Cheatham, Christopher Hill, Yang Li, S. Michael Yu
The triple-helical structure of collagen, responsible for collagen’s remarkable biological and mechanical properties, has inspired both basic and applied research in synthetic peptide mimetics for decades. Since non-proline amino acids weaken the triple helix, the cyclic structure of proline has been considered necessary, and functional collagen mimetic peptides (CMPs) with diverse sidechains have been difficult to produce. Here we show that N-substituted glycines (N-glys), also known as peptoid residues, exhibit a general triple-helical propensity similar to or greater than proline, allowing synthesis of thermally stable triple-helical CMPs with unprecedented sidechain diversity. We found that the N-glys stabilize the triple helix by sterically promoting the preorganization of individual CMP chains into the polyproline-II helix conformation. Our findings were supported by the crystal structures of two atomic-resolution N-gly-containing CMPs, as well as experimental and computational studies spanning more than 30 N-gly-containing peptides. We demonstrated that N-gly sidechains with diverse exotic moieties including a ‘click’-able alkyne and a photo-sensitive sidechain can be incorporated into stable triple helices, enabling functional applications such spatio-temporal control of cell adhesion and migration on a gelatin matrix. The folding principles discovered in this study open up opportunities for a new generation of collagen mimetic therapeutics and materials with extraordinary properties.

History

Email Address of Submitting Author

yang.d.li@utah.edu

Institution

University of Utah

Country

USA

ORCID For Submitting Author

0000-0003-4729-7860

Declaration of Conflict of Interest

no conflict of interest

Version Notes

20200905_01

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