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Inhibition of bacterial RNase P by aminoglycoside–arginine conjugates
Author(s) -
Eubank Timothy D.,
Biswas Roopa,
Jovanovic Milan,
Litovchick Alexander,
Lapidot Aviva,
Gopalan Venkat
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03322-1
Subject(s) - rnase p , rna , arginine , biology , activator (genetics) , transfer rna , aminoglycoside , chemistry , biochemistry , gene , antibiotics , amino acid
The potential of RNAs and RNA–protein (RNP) complexes as drug targets is currently being explored in various investigations. For example, a hexa‐arginine derivative of neomycin (NeoR) and a tri‐arginine derivative of gentamicin (R3G) were recently shown to disrupt essential RNP interactions between the trans ‐activator protein (Tat) and the Tat‐responsive RNA ( trans ‐activating region) in the human immunodeficiency virus (HIV) and also inhibit HIV replication in cell culture. Based on certain structural similarities, we postulated that NeoR and R3G might also be effective in disrupting RNP interactions and thereby inhibiting bacterial RNase P, an essential RNP complex involved in tRNA maturation. Our results indicate that indeed both NeoR and R3G inhibit RNase P activity from evolutionarily divergent pathogenic bacteria and do so more effectively than they inhibit partially purified human RNase P activity.