Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential

Qiu, Ruomeng; Sasselli, Ivan R.; Álvarez, Zaida; Sai, Hiroaki; Ji, Wei; Palmer, Liam C.; Stupp, Samuel I.

doi:10.1021/jacs.2c00433

Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential

Journal Article · Thu Mar 17 00:00:00 EDT 2022 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.2c00433· OSTI ID:1909454

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Northwestern Univ., Evanston, IL (United States)

Supramolecular peptide chemistry offers a versatile strategy to create chemical systems useful as new biomaterials with potential to deliver nearly 1000 known candidate peptide therapeutics or integrate other types of bioactivity. Here, we report on the co-assembly of lipidated β-sheet-forming peptides with soluble short peptides, yielding supramolecular copolymers with various degrees of internal order. At low peptide concentrations, the co-monomer is protected by lodging within internal aqueous compartments and stabilizing internal β-sheets formed by the lipidated peptides. At higher concentrations, the peptide copolymerizes with the lipidated peptide and disrupts the β-sheet secondary structure. The thermodynamic metastability of the co-assembly in turn leads to the spontaneous release of peptide monomers and thus serves as a potential mechanism for drug delivery. We demonstrated the function of these supramolecular systems using a drug candidate for Alzheimer’s disease and found that the copolymers enhance neuronal cell viability when the soluble peptide is released from the assemblies.

View Accepted Manuscript (DOE)

Research Organization:: Energy Frontier Research Centers (EFRC) (United States). Center for Bio-Inspired Energy Science (CBES)

Sponsoring Organization:: KU Leuven; National Institutes of Health (NIH); National Science Foundation (NSF); Paralyzed Veterans of America (PVA) Research Foundation; Research Foundation Flanders (FWO); USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357; SC0020884

Other Award/Contract Number:: PVA17RF0008
12G2718N
JUMO-15-0514
DMR-1720139
ECCS-2025633
P30 CA060553
1S10OD012016-01
1S10RR019071-01A1

OSTI ID:: 1909454

Alternate ID(s):: OSTI ID: 1861854
OSTI ID: 1863059

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 12 Vol. 144; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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