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Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties.

ABSTRACT: Ribosome-inactivating proteins (RIPs) are N-glycosidases, which depurinate a specific adenine residue in the conserved ?-sarcin/ricin loop (?-SRL) of rRNA. This loop is important for anchoring elongation factor (EF-G for prokaryote or eEF2 for eukaryote) in mRNA translocation. Translation is inhibited after the attack. RIPs therefore may have been applied for anti-cancer, and anti-virus and other therapeutic applications. The main obstacles of treatment with RIPs include short plasma half-life, non-selective cytotoxicity and antigenicity. This review focuses on the strategies used to improve the pharmacological properties of RIPs on human immunodeficiency virus (HIV) and cancers. Coupling with polyethylene glycol (PEG) increases plasma time and reduces antigenicity. RIPs conjugated with antibodies to form immunotoxins increase the selective toxicity to target cells. The prospects for future development on the engineering of RIPs for improving their pharmacological properties are also discussed.

SUBMITTER: Lu JQ

PROVIDER: S-EPMC7150887 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties.

Lu Jia-Qi JQ Zhu Zhen-Ning ZN Zheng Yong-Tang YT Shaw Pang-Chui PC

Toxins 20200309 3

Ribosome-inactivating proteins (RIPs) are N-glycosidases, which depurinate a specific adenine residue in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. This loop is important for anchoring elongation factor (EF-G for prokaryote or eEF2 for eukaryote) in mRNA translocation. Translation is inhibited after the attack. RIPs therefore may have been applied for anti-cancer, and anti-virus and other therapeutic applications. The main obstacles of treatment with RIPs include short plasma half-life, ...[more]

PMID: 32182799

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