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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Aminoglycoside Mimetics as Small-Molecule Drugs Targeting RNA

Author(s): Xin-Shan Ye and Li-He Zhang

Volume 9, Issue 9, 2002

Page: [929 - 939] Pages: 11

DOI: 10.2174/0929867024606740

Price: $65

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Abstract

The potential of RNA as a new drug target has recently come to the fore, with the recognition that RNA molecules can adopt complex three-dimensional structures that, as with proteins, enable the design of specific ligands. Another reason for the present interest comes from the fact that many pathogenic agents, such as retroviruses, encode their genetic information in RNA strands. Unfortunately, the high toxicity and rapid emergence of high-level resistance have severely limited the usefulness of naturally occurring aminoglycoside antibiotics. To tackle these problems, it is an important concern to design new synthetic compounds with smaller, simpler structures which possess higher RNA binding affinity, better selectivity, better antibiotic activity, and stronger resistance against the aminoglycoside-modifying enzymes compared to their parent structures. Here, we will attempt a survey of current efforts to develop aminoglycoside mimetics or derivatives that target RNA. The latest advances in this field including rational design, synthetic strategy, and structure activity relationships are reviewed.

Keywords: aminoglycoside, viral rna


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