Dataset Information

Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation.

ABSTRACT: To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG5k or PEG20k. The resultant PEG derivatives of MOD variants were examined for ribosome-inactivating activity, circulating half-life and immunogenicity. Our results showed that MOD-PEG conjugates had two- to five-fold lower biological activity compared to the wild-type. Mutation of the two sites respectively did not decrease the anti-MOD IgG and IgE level in mice, but the conjugation of PEG did dramatically reduce the antigenicity. Furthermore, pharmacokinetics studies demonstrated that attachment of PEG20k prolonged the plasma half-life by five-fold for MOD-K78C and 17-fold for MOD-K264C, respectively. The site-specific mutation together with PEGylation therefore generated MOD derivatives with improved pharmacological properties.

SUBMITTER: Au KY

PROVIDER: S-EPMC5086658 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation.

Au Ka-Yee KY Shi Wei-Wei WW Qian Shuai S Zuo Zhong Z Shaw Pang-Chui PC

Toxins 20161017 10

To improve the pharmacological properties of maize ribosome-inactivating protein (maize RIP) for targeting HIV-infected cells, the previously engineered TAT-fused active form of maize RIP (MOD) was further engineered for cysteine-directed PEGylation. In this work, two potential antigenic sites, namely Lys-78 and Lys-264, were identified. They were mutated to cysteine residue and conjugated with PEG<sub>5k</sub> or PEG<sub>20k</sub>. The resultant PEG derivatives of MOD variants were examined for ...[more]

PMID: 27763506

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Project description:BackgroundPhytochemicals and other molecules in foods elicit positive health benefits, often by poorly established or unknown mechanisms. While there is a wealth of data on the biological and biophysical properties of drugs and therapeutic compounds, there is a notable lack of similar data for compounds commonly present in food. Computational methods for high-throughput identification of food compounds with specific biological effects, especially when accompanied by relevant food composition data, could enable more effective and more personalized dietary planning. We have created a machine learning-based tool (PhyteByte) to leverage existing pharmacological data to predict bioactivity across a comprehensive molecular database of foods and food compounds.ResultsPhyteByte uses a cheminformatic approach to structure-based activity prediction and applies it to uncover the putative bioactivity of food compounds. The tool takes an input protein target and develops a random forest classifier to predict the effect of an input molecule based on its molecular fingerprint, using structure and activity data available from the ChEMBL database. It then predicts the relevant bioactivity of a library of food compounds with known molecular structures from the FooDB database. The output is a list of food compounds with high confidence of eliciting relevant biological effects, along with their source foods and associated quantities in those foods, where available. Applying PhyteByte to the human PPARG gene, we identified irigenin, sesamin, fargesin, and delta-sanshool as putative agonists of PPARG, along with previously identified agonists of this important metabolic regulator.ConclusionsPhyteByte identifies food-based compounds that are predicted to interact with specific protein targets. The identified relationships can be used to prioritize food compounds for experimental or epidemiological follow-up and can contribute to the rapid development of precision approaches to new nutraceuticals as well as personalized dietary planning.

Dataset Information

Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation.

Publications

Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation.

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