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Article
| Open Access
Disrupting the α-synuclein-ESCRT interaction with a peptide inhibitor mitigates neurodegeneration in preclinical models of Parkinson’s disease
ESCRT-III is involved in the endolysosomal system and disturbed in neurodegenerative diseases. Here the authors show that disruption of an interaction between ESCRT-III member CHMP2B and α-synuclein by a peptide inhibitor mitigates neurodegeneration in Parkinson’s disease models.
- Satra Nim
- , Darren M. O’Hara
- & Philip M. Kim
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Article
| Open Access
Efficient in planta production of amidated antimicrobial peptides that are active against drug-resistant ESKAPE pathogens
Antimicrobial peptides (AMPs) are next-generation antibiotics that can be used to combat drugresistant pathogens. Here, the authors report efficient production of bioactive amidated AMPs by transient expression in Nicotiana benthamiana line expressing the mammalian enzyme peptidylglycine α-amidating mono-oxygenase.
- Shahid Chaudhary
- , Zahir Ali
- & Magdy Mahfouz
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Article
| Open Access
Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs
Inhibiting thrombosis without inducing bleeding is a major challenge for anticoagulant agents. Here the authors describe a synthetic FXIIa inhibitor able to efficiently prevent thrombosis in mice and suppress coagulation in artificial lungs in rabbits without increasing the risk of bleeding.
- Jonas Wilbs
- , Xu-Dong Kong
- & Christian Heinis
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Article
| Open Access
Reverse engineering synthetic antiviral amyloids
Some human amyloid proteins have been shown to interact with viral proteins, suggesting that they may have potential as therapeutic agents. Here the authors design synthetic amyloids specific for influenza A and Zika virus proteins, respectively, and show that they can inhibit viral replication.
- Emiel Michiels
- , Kenny Roose
- & Joost Schymkowitz
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Article
| Open Access
Structure-guided design of pure orthosteric inhibitors of αIIbβ3 that prevent thrombosis but preserve hemostasis
Current inhibitors of platelet integrin αIIbβ3 cause excessive bleeding, which limited their clinical use in cardiac patients. Here the authors design pure orthosteric αIIbβ3 inhibitors that prevent platelet aggregation and thrombosis without causing bleeding in humanized mouse models of thrombosis
- Brian D. Adair
- , José L. Alonso
- & M. Amin Arnaout
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Article
| Open Access
Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets
Pathologies related to protein:protein interaction are hard to treat but cystine-dense peptides have the potential to disrupt such interactions. Here the authors develop a high-diversity mammalian cell screen for cystine-dense peptides with drug potential and use it to identify a YAP:TEAD inhibitor.
- Zachary R. Crook
- , Gregory P. Sevilla
- & James M. Olson
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Article
| Open Access
Endosomal NOX2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy
Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.
- Eunice E. To
- , Ross Vlahos
- & Stavros Selemidis
Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function