Targeting Bacillus anthracis toxicity with a genetically selected inhibitor of the PA/CMG2 protein-protein interaction

Male, Abigail L.; Forafonov, Fedor; Cuda, Francesco; Zhang, Gong; Zheng, Siqi; Oyston, Petra C. F.; Chen, Peng R.; Williamson, E. Diane; Tavassoli, Ali

doi:10.1038/s41598-017-03253-3

Cited by 20 publications

(21 citation statements)

References 32 publications

(41 reference statements)

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“…The Tavassoli group screened for protein-protein interaction inhibitors using the SICLOPPS cyclic hexapeptide library. Their top 3 hits all contained stop codons, implying that linear peptides are the better for their target Bacillus anthracis protective antigen (Male et al ., 2017).…”

Section: The Role Of Cyclic Peptides In Therapeuticsmentioning

confidence: 99%

Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

Choi

Joo

2020

Biomolecules & Therapeutics

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Notable progress has been made in the therapeutic and research applications of cyclic peptides since our previous review. New drugs based on cyclic peptides are entering the market, such as plecanatide, a cyclic peptide approved by the United States Food and Drug Administration in 2017 for the treatment of chronic idiopathic constipation. In this review, we discuss recent developments in stapled peptides, prepared with the use of chemical linkers, and bicyclic/tricyclic peptides with more than two rings. These have widespread applications for clinical and research purposes: imaging, diagnostics, improvement of oral absorption, enzyme inhibition, development of receptor agonist/antagonist, and the modulation of protein-protein interaction or protein-RNA interaction. Many cyclic peptides are expected to emerge as therapeutics and biochemical tools.

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Section: The Role Of Cyclic Peptides In Therapeuticsmentioning

confidence: 99%

Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

Choi

Joo

2020

Biomolecules & Therapeutics

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“…This procedure removes any false positives with chromosomal mutations that conferred the growth advantage. The substrate specificity of the hits was also assessed using another RTHS strain that was identical to the p6–UEV strain, except that p6 and UEV were replaced with an unrelated PPI (human CMG2 interacting with Bacillus anthracis protective antigen) 39 ; peptides showing inhibition of this unrelated PPI were discarded as they were either non-specific inhibitors, or targeted other components of the RTHS ( Supplementary Fig. 8b ).…”

Section: Resultsmentioning

confidence: 99%

A lanthipeptide library used to identify a protein–protein interaction inhibitor

et al. 2018

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We describe the production and screening of a genetically encoded library of 106 lanthipeptides in Escherichia coli using the substrate-tolerant lanthipeptide synthetase ProcM. This plasmidencoded library was combined with a bacterial reverse two-hybrid system for the interaction of the HIV p6 protein with the UEV domain of the human TSG101 protein, a critical protein–protein interaction for HIV budding from infected cells. Using this approach, we identified an inhibitor of this interaction from the lanthipeptide library, whose activity was verified in vitro and in cell-based virus-like particle budding assays. Given the variety of lanthipeptide backbone scaffolds that may be produced with ProcM, this method may be used for the generation of genetically encoded libraries of natural product-like lanthipeptides containing substantial structural diversity. Such libraries may be combined with any cell-based assay for the identification of lanthipeptides with new biological activities.

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“…antharacis protective antigen and the human CMG2 receptor that is essential for the cellular uptake of anthrax lethal and edema toxins with a K D of 38.2 µM (Male et al, 2017). They have also enabled the development of cell-permeable inhibitors of the HIV Gag protein interaction with human TSG101, essential for HIV virus budding with a K D of 11.9 µM (Lennard et al,FIGURE 11 | General scheme of the RaPID system.…”

Section: Protein Splicing Methodsmentioning

confidence: 99%

Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies

et al. 2020

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Backbone macrocyclic structures are often found in diverse bioactive peptides and contribute to greater conformational rigidity, peptidase resistance, and potential membrane permeability compared to their linear counterparts. Therefore, such peptide scaffolds are an attractive platform for drug-discovery endeavors. Recent advances in synthetic methods for backbone macrocyclic peptides have enabled the discovery of novel peptide drug candidates against diverse targets. Here, we overview recent technical advancements in the synthetic methods including 1) enzymatic synthesis, 2) chemical synthesis, 3) split-intein circular ligation of peptides and proteins (SICLOPPS), and 4) in vitro translation system combined with genetic code reprogramming. We also discuss screening methodologies compatible with those synthetic methodologies, such as one-beads one-compound (OBOC) screening compatible with the synthetic method 2, cell-based assay compatible with 3, limiting-dilution PCR and mRNA display compatible with 4.

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Targeting Bacillus anthracis toxicity with a genetically selected inhibitor of the PA/CMG2 protein-protein interaction

Cited by 20 publications

References 32 publications

Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

Recent Trends in Cyclic Peptides as Therapeutic Agents and Biochemical Tools

A lanthipeptide library used to identify a protein–protein interaction inhibitor

Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible With Screening Technologies

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