Peptide Logic Circuits Based on Chemoenzymatic Ligation for Programmable Cell Apoptosis

Li, Yong; Sun, Shaodong; Lin, Fan; Hu, Shanfang; Huang, Yan; Zhang, Ke; Nie, Zhou; Yao, Shanshan

doi:10.1002/ange.201708327

Cited by 8 publications

(2 citation statements)

References 75 publications

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“…Second, we examined whether the expressed SrtA was catalytically active as expected. According to the previously reported method, 39 its transpeptidase activity can be detected by using fluorophore and quencher-modified peptide probes (P F and P Q ). As shown in Figure S3, after P F and P Q were mixed with SrtA, the fluorescence intensity of the solution was quenched by 27.2% compared to that of without SrtA.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Transpeptidation-Mediated Assembly of Tripartite Split Green Fluorescent Protein for Label-Free Assay of Sortase Activity

et al. 2018

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Transpeptidation of surface proteins catalyzed by the transpeptidase sortase plays a critical role in the infection process of Gram-positive pathogen, and probing sortase activity and screening its inhibitors are of great significance to fundamental biological research and pharmaceutical development, especially novel antivirulence drug design. Herein, we developed a novel fluorescent biosensor to detect sortase activity based on a transpeptidation-triggered assembly of tripartite split green fluorescent protein (split GFP). Peptide P, composed the 10th β-sheet of GFP (GFP10) and the sortase A (SrtA) recognition sequence (LPETX), and peptide P, the 11th β-sheet of GFP (GFP11) with oligoglycine at N-terminal, were designed and synthesized, respectively. Existence of SrtA enables P and P to ligate into one peptide, which could spontaneously bind to GFP1-9 (the 1st to 9th β-sheets of GFP) and assemble into functional GFP. Thus, the sortase-catalyzed transpeptidation can switch on the fluorescence signal of GFP. The method was successfully applied to detect SrtA activity with a low detection limit of 0.16 nM and for its inhibition measurement. Moreover, the feasibility of the proposed assay was further expanded to detect SrtA in human blood and further Gram-positive pathogens analysis in frozen food. Our method, using tripartite split GFP as a readout, is facile, label-free, and sensitive and exhibits great potential as a promising platform for sortase detection and inhibitor screening.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Transpeptidation-Mediated Assembly of Tripartite Split Green Fluorescent Protein for Label-Free Assay of Sortase Activity

et al. 2018

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“…Molecular devices with enzymes as processors were adapted to perform logical computing with peptide sequences as inputs into biochemical circuits within cells. In this demonstration by Li et al., [ 67 ] mammalian cell apoptosis was programmed by a series of peptide‐based logic circuits which was interfaced with another regulatory circuit that sensed the expression of secreted biomarkers and triggered apoptosis in cancer cells. Logic operations such as AND (where the presence of both input molecules was essential to initiate the reaction), OR (where the presence of one of the input peptides would suffice to initiate apoptosis) and INHIBIT (where the presence of only one input would initiate cell death) were performed using suitable peptide sequences.…”

Section: The Era Of Molecular Networkmentioning

confidence: 99%

The art of molecular computing: Whence and whither

Gangadharan

Raman

2021

BioEssays

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An astonishingly diverse biomolecular circuitry orchestrates the functioning machinery underlying every living cell. These biomolecules and their circuits have been engineered not only for various industrial applications but also to perform other atypical functions that they were not evolved for-including computation. Various kinds of computational challenges, such as solving NP-complete problems with many variables, logical computation, neural network operations, and cryptography, have all been attempted through this unconventional computing paradigm. In this review, we highlight key experiments across three different ''eras'' of molecular computation, beginning with molecular solutions, transitioning to logic circuits and ultimately, more complex molecular networks. We also discuss a variety of applications of molecular computation, from solving NP-hard problems to self-assembled nanostructures for delivering molecules, and provide a glimpse into the exciting potential

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Biocomputing for Portable, Resettable, and Quantitative Point‐of‐Care Diagnostics: Making the Glucose Meter a Logic‐Gate Responsive Device for Measuring Many Clinically Relevant Targets

Zhang

2018

Angewandte Chemie

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It is recognized that biocomputing can provide intelligent solutions to complex biosensing projects.H owever, it remains challenging to transform biomolecular logic gates into convenient, portable,r esettable and quantitative sensing systems for point-of-care (POC) diagnostics in alow-resource setting.T oo vercome these limitations,t he first design of biocomputing on personal glucose meters (PGMs) is reported, which utilizes glucose and the reduced form of nicotinamide adenine dinucleotide as signal outputs,DNAzymes and protein enzymes as building blocks,a nd demonstrates ag eneral platform for installing logic-gate responses (YES,N OT, INHIBIT,N OR, NAND,a nd OR) to av ariety of biological species,s uch as cations (Na + ), anions (citrate), organic metabolites (adenosine diphosphate and adenosine triphosphate) and enzymes (pyruvate kinase,a lkaline phosphatase, and alcohol dehydrogenases). Ac oncatenated logical gate platform that is resettable is also demonstrated. The system is highly modular and can be generally applied to POC diagnostics of many diseases,s uch as hyponatremia, hypernatremia, and hemolytic anemia. In addition to broadening the clinical applications of the PGM, the method reported opens anew avenue in biomolecular logic gates for the development of intelligent POC devices for on-site applications. Figure 4. "Concatenated" logic gate using both NADH and glucose as the output. a) Scheme of the biocatalyticcascade with multiple inputs and outputs. b) The PGM response of repeated switches between "off" and "on" states by adding appropriate inputs of enzyme substrates and coenzymes.

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Peptide Logic Circuits Based on Chemoenzymatic Ligation for Programmable Cell Apoptosis

Cited by 8 publications

References 75 publications

Transpeptidation-Mediated Assembly of Tripartite Split Green Fluorescent Protein for Label-Free Assay of Sortase Activity

Transpeptidation-Mediated Assembly of Tripartite Split Green Fluorescent Protein for Label-Free Assay of Sortase Activity

The art of molecular computing: Whence and whither

Biocomputing for Portable, Resettable, and Quantitative Point‐of‐Care Diagnostics: Making the Glucose Meter a Logic‐Gate Responsive Device for Measuring Many Clinically Relevant Targets

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