Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation
AbstractTo 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. View Full-Text
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Au, K.-Y.; Shi, W.-W.; Qian, S.; Zuo, Z.; Shaw, P.-C. Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation. Toxins 2016, 8, 298.
Au K-Y, Shi W-W, Qian S, Zuo Z, Shaw P-C. Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation. Toxins. 2016; 8(10):298.Chicago/Turabian Style
Au, Ka-Yee; Shi, Wei-Wei; Qian, Shuai; Zuo, Zhong; Shaw, Pang-Chui. 2016. "Improvement of the Pharmacological Properties of Maize RIP by Cysteine-Specific PEGylation." Toxins 8, no. 10: 298.
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