Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential

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

doi:10.1021/jacs.2c00433

Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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. We report here 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.

Original language	English (US)
Pages (from-to)	5562-5574
Number of pages	13
Journal	Journal of the American Chemical Society
Volume	144
Issue number	12
DOIs	https://doi.org/10.1021/jacs.2c00433
State	Published - Mar 30 2022

Funding

This work was primarily supported by the Center for Regenerative Nanomedicine at the Simpson Querrey Institute for BioNanotechnology. Additional support for infrared spectroscopy studies with isotopic labels was provided by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under award no. DE-SC0020884. We also thank the Paralyzed Veterans of America (PVA) Research Foundation fellowship PVA17RF0008 (Z.A.). We also acknowledge a postdoctoral fellowship from Research Foundation Flanders (FWO) Postdoctoral Mandates 12G2718N and a Junior Mobility Travel Grant from KU Leuven (JUMO-15-0514) (W.J.). We acknowledge use of the following core facilities at Northwestern University: the Peptide Synthesis Core Facility and the Analytical bioNanoTechnology Core Facility of the Simpson Querrey Institute, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), Keck Biophysics Facility, a shared resource of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University supported in part by the NCI Cancer Center Support grant #P30 CA060553, the Keck-II facility and the BioCryo facility of Northwestern University’s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), and the IMSERC NMR facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), NIH 1S10OD012016-01/1S10RR019071-01A1, Northwestern University,the IIN, and Northwestern’s MRSEC program (NSF DMR-1720139). Confocal imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. X-ray experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, The Dow Chemical Company, and DuPont de Nemours, Inc. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under contract no. DE-AC02-06CH11357. Data were collected using an instrument funded by the National Science Foundation under award number 0960140. This research was supported in part by the computational resources and staff contributions provided by the Quest High-Performance Computing Facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. We thank Mark Seniw for providing molecular graphics.

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/jacs.2c00433

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@article{b5e7302174424e47b97352bf61161ac6,

title = "Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential",

abstract = "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. We report here 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.",

author = "Ruomeng Qiu and Sasselli, {Ivan R.} and Zaida {\'A}lvarez and Hiroaki Sai and Wei Ji and Palmer, {Liam C.} and Stupp, {Samuel I.}",

note = "Funding Information: This work was primarily supported by the Center for Regenerative Nanomedicine at the Simpson Querrey Institute for BioNanotechnology. Additional support for infrared spectroscopy studies with isotopic labels was provided by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under award no. DE-SC0020884. We also thank the Paralyzed Veterans of America (PVA) Research Foundation fellowship PVA17RF0008 (Z.A.). We also acknowledge a postdoctoral fellowship from Research Foundation Flanders (FWO) Postdoctoral Mandates 12G2718N and a Junior Mobility Travel Grant from KU Leuven (JUMO-15-0514) (W.J.). We acknowledge use of the following core facilities at Northwestern University: the Peptide Synthesis Core Facility and the Analytical bioNanoTechnology Core Facility of the Simpson Querrey Institute, which has current support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), Keck Biophysics Facility, a shared resource of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University supported in part by the NCI Cancer Center Support grant #P30 CA060553, the Keck-II facility and the BioCryo facility of Northwestern University{\textquoteright}s NUANCE Center, which has received support from the SHyNE Resource (NSF ECCS-2025633), and the IMSERC NMR facility at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-2025633), NIH 1S10OD012016-01/1S10RR019071-01A1, Northwestern University,the IIN, and Northwestern{\textquoteright}s MRSEC program (NSF DMR-1720139). Confocal imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. X-ray experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, The Dow Chemical Company, and DuPont de Nemours, Inc. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by the Argonne National Laboratory under contract no. DE-AC02-06CH11357. Data were collected using an instrument funded by the National Science Foundation under award number 0960140. This research was supported in part by the computational resources and staff contributions provided by the Quest High-Performance Computing Facility at Northwestern University, which is jointly supported by the Office of the Provost, the Office for Research, and Northwestern University Information Technology. We thank Mark Seniw for providing molecular graphics. Publisher Copyright: {\textcopyright} 2022 American Chemical Society.",

year = "2022",

month = mar,

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doi = "10.1021/jacs.2c00433",

language = "English (US)",

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AU - Palmer, Liam C.

AU - Stupp, Samuel I.

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N2 - 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. We report here 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.

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Supramolecular Copolymers of Peptides and Lipidated Peptides and Their Therapeutic Potential

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