Peptide supramolecular materials for therapeutics

Sato, Kohei; Hendricks, Mark P.; Palmer, Liam C.; Stupp, Samuel I.

doi:10.1039/c7cs00735c

Cited by 240 publications

(190 citation statements)

References 50 publications

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“…Meanwhile, the delivery of therapeutic peptides is known to be challenging concerning their short half-life due to the rapid proteolytic degradation and short circulation time due to the low molecular weight. 23,24 These could be potentially overcome by covalently grafting oligopeptides at the side chains of peptide brush polymers, 25 or integrating them onto peptide amphiphiles 26 or PEGylation 27 .…”

Section: Design Of Oligopeptide Inhibitormentioning

confidence: 99%

The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding

Qiao

Cruz

2020

Preprint

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The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. A negatively charged tetrapeptide (GluGluLeuGlu) is then designed to neutralize the positively charged arginine on the polybasic cleavage sites. We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection. TOC:The SARS-CoV-2 spike protein-ACE2 complex showing the polybasic cleavage sites

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Section: Design Of Oligopeptide Inhibitormentioning

confidence: 99%

The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding

Qiao

Cruz

2020

Preprint

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“…The attachment of lipophilic moieties to hydrophilic drug molecules enhances the bioavailability of the therapeutic agents . Despite that various peptides have been modified by anchoring of hydrophobic acyl chains (lipidated peptides), the resulting structures have scarcely been composed of neuroprotective molecules . At variance, extensive research has been reported on self‐assembly of antimicrobial and anticancer peptides and the destabilization of lipid membranes …”

Section: Introductionmentioning

confidence: 99%

Pep‐Lipid Cubosomes and Vesicles Compartmentalized by Micelles from Self‐Assembly of Multiple Neuroprotective Building Blocks Including a Large Peptide Hormone PACAP‐DHA

et al. 2019

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Structural control over design and formation of self‐assembled nanomaterials for neuroprotection and neuroregeneration is crucial for their application in nanomedicine. Here a synthetic construct of the pituitary adenylate cyclase‐activating polypeptide (PACAP38) coupled to a docosahexaenoic acid (DHA: an ω‐3 polyunsaturated fatty acid (PUFA)) is designed towards the creation of compartmentalized liquid crystalline assemblies of neuroprotective compounds. The hormone PACAP38 is a ligand of the class B PAC1 G‐protein‐coupled receptor (GPCR), whereas DHA is a lipid trophic factor. The lipidated peptide PACAP‐DHA is co‐assembled into hierarchical nanostructures elaborated from hybrid vesicle‐micelle reservoirs as well into PEGylated cubosomes composed of multiple neuroprotective building blocks. The resulting nanostructures are determined by synchrotron small‐angle X‐ray scattering (BioSAXS) and cryogenic transmission electron microscopy (cryo‐TEM). Multicompartment topologies are obtained in a two‐fold approach: (i) intriguing compartmentalized vesicles, which embed pep‐lipid micelles forming nanopatterns, and (ii) multidomain pep‐lipid cubosomes. Both kinds of topologies are favorable for sustained‐release applications in combination therapies of neurodegeneration. The organizational complexity of the scaffolds involving the lipidated high‐molecular weight peptide hormone is beyond the one that has been reached with small lipid‐like peptide surfactants.

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“…Short synthetic peptides derived from ECM proteins retain the integrin-binding function, thus are attractive in the design of materials. For example, the Stupp group has developed bioactive peptide amphiphiles (PA) for regenerative medicine applications (Boekhoven and Stupp, 2014;Hendricks et al, 2017;Sato et al, 2018). The RGDS sequence has been attached to PA to induce integrin-mediated adhesion, spreading or migration of fibroblasts, breast cancer cells, and bone marrow mononuclear cells in vitro (Storrie et al, 2007;Webber et al, 2010;Zhou et al, 2019).…”

Section: Interactions Of Ecm With Cell Receptorsmentioning

confidence: 99%

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

Hwang

Sullivan

Kiick

2020

Front. Bioeng. Biotechnol.

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The use of drug delivery vehicles to improve the efficacy of drugs and to target their action at effective concentrations over desired periods of time has been an active topic of research and clinical investigation for decades. Both synthetic and natural drug delivery materials have facilitated locally controlled as well as targeted drug delivery. Extracellular matrix (ECM) molecules have generated widespread interest as drug delivery materials owing to the various biological functions of ECM. Hydrogels created using ECM molecules can provide not only biochemical and structural support to cells, but also spatial and temporal control over the release of therapeutic agents, including small molecules, biomacromolecules, and cells. In addition, the modification of drug delivery carriers with ECM fragments used as cell-binding ligands has facilitated celltargeted delivery and improved the therapeutic efficiency of drugs through interaction with highly expressed cellular receptors for ECM. The combination of ECM-derived hydrogels and ECM-derived ligand approaches shows synergistic effects, leading to a great promise for the delivery of intracellular drugs, which require specific endocytic pathways for maximal effectiveness. In this review, we provide an overview of cellular receptors that interact with ECM molecules and discuss examples of selected ECM components that have been applied for drug delivery in both local and systemic platforms. Finally, we highlight the potential impacts of utilizing the interaction between ECM components and cellular receptors for intracellular delivery, particularly in tissue regeneration applications.

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Peptide supramolecular materials for therapeutics

Cited by 240 publications

References 50 publications

The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding

The Distal Polybasic Cleavage Sites of SARS-CoV-2 Spike Protein Enhance Spike Protein-ACE2 Binding

Pep‐Lipid Cubosomes and Vesicles Compartmentalized by Micelles from Self‐Assembly of Multiple Neuroprotective Building Blocks Including a Large Peptide Hormone PACAP‐DHA

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

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