Attenuating HIV Tat/TAR-mediated protein expression by exploring the side chain length of positively charged residues

Please use this identifier to cite or link to this item: https://ir.lib.ncu.edu.tw/handle/987654321/103111

Title:	Attenuating HIV Tat/TAR-mediated protein expression by exploring the side chain length of positively charged residues
Authors:	簡汎清;Wu, Cheng-Hsun;Chen, Yi-Ping;Liu, Shing-Lung;Chien, Fan-Ching;Mou, Chung-Yuan;Cheng, Richard P
Contributors:	理學院光電科學與工程學系
Date:	2015-01-01
Issue Date:	2026-04-23 11:23:32 (UTC+8)
Publisher:	Royal Society of Chemistry
Abstract:	摘要： RNA is a drug target involved in diverse cellular functions and viral processes. Molecules that inhibit the HIV TAR RNA-Tat protein interaction may attenuate Tat/TAR-dependent protein expression and potentially serve as anti-HIV therapeutics. By incorporating positively charged residues with mixed side chain lengths, we designed peptides that bind TAR RNA with enhanced intracellular activity. Tat-derived peptides that were individually substituted with positively charged residues with varying side chain lengths were evaluated for TAR RNA binding. Positively charged residues with different side chain lengths were incorporated at each Arg and Lys position in the Tat-derived peptide to enhance TAR RNA binding. The resulting peptides showed enhanced TAR RNA binding affinity, cellular uptake, nuclear localization, proteolytic resistance, and inhibition of intracellular Tat/TAR-dependent protein expression compared to the parent Tat-derived peptide with no cytotoxicity. Apparently, the enhanced inhibition of protein expression by these peptides was not determined by RNA binding affinity, but by proteolytic resistance. Despite the high TAR binding affinity, a higher binding specificity would be necessary for practical purposes. Importantly, altering the positively charged residue side chain length should be a viable strategy to generate potentially useful RNA-targeting bioactive molecules. Altering amino acid side chain lengths enhanced multiple bioactivities and inhibited intracellular protein production. 出版日期： 2015-11-11 資源來源： Royal Society of Chemistry 識別號： ISSN: 1477-0520 識別號： EISSN: 1477-0539 識別號： DOI: 10.1039/c5ob01729g
Appears in Collections:	[Department of Optics and Photonics] journal & Dissertation

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