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Toxins 2016, 8(10), 298; doi:10.3390/toxins8100298

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

1
Centre for Protein Science and Crystallography, School of Life Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
2
School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
*
Author to whom correspondence should be addressed.
Academic Editors: Julien Barbier and Daniel Gillet
Received: 7 September 2016 / Revised: 4 October 2016 / Accepted: 11 October 2016 / Published: 17 October 2016
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
View Full-Text   |   Download PDF [1780 KB, uploaded 17 October 2016]   |  

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. View Full-Text
Keywords: MOD; PEGylation; antigenicity; pharmacokinetics study; circulation half-life; antibody induction MOD; PEGylation; antigenicity; pharmacokinetics study; circulation half-life; antibody induction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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.

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