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De Novo Design of Integrin α5β1 Modulating Proteins for Regenerative Medicine.
bioRxiv
July 2024
Department of Biochemistry, University of Washington, Seattle, WA, USA.
Article Synopsis
- Integrin α5β1 plays a key role in how cells attach and move, making it important for development and healing, with its binding proteins being useful in regenerative medicine.* -
- Researchers developed custom proteins called NeoNectins that specifically target and stabilize the active form of α5β1, leading to improved cell attachment and spread in lab tests.* -
- When used on titanium surfaces and in 3D hydrogels, NeoNectins showed better results compared to traditional options in boosting tissue integration and bone growth in animal studies, highlighting their potential in biomedicine.*
Preclinical proof of principle for orally delivered Th17 antagonist miniproteins.
Cell
August 2024
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address:
Interleukin (IL)-23 and IL-17 are well-validated therapeutic targets in autoinflammatory diseases. Antibodies targeting IL-23 and IL-17 have shown clinical efficacy but are limited by high costs, safety risks, lack of sustained efficacy, and poor patient convenience as they require parenteral administration. Here, we present designed miniproteins inhibiting IL-23R and IL-17 with antibody-like, low picomolar affinities at a fraction of the molecular size.
View Article and Find Full Text PDFNematicidal Activity of Cyclotides: Toxicity Against .
J Nat Prod
May 2023
Institute for Molecular Bioscience, Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland 4072, Australia.
Cyclotides are a unique family of stable and cyclic mini-proteins found in plants that have nematicidal and anthelmintic activities. They are distributed across the Rubiaceae, Violaceae, Fabaceae, Cucurbitaceae, and Solanaceae plant families, where they are posited to act as protective agents against pests. In this study, we tested the nematicidal properties of extracts from four major cyclotide-producing plants, , , , and , against the free-living model nematode .
View Article and Find Full Text PDFMultivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice.
Sci Transl Med
May 2022
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture.
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