Inhibition of bacterial RNase P by aminoglycoside-arginine conjugates.
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.
Eubank
Timothy D
TD
Department of Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Biswas
Roopa
R
Jovanovic
Milan
M
Litovchick
Alexander
A
Lapidot
Aviva
A
Gopalan
Venkat
V
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology*; D003001:Cloning, Molecular; D004722:Endoribonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins; D005601:Framycetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D020035:Holoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007612:Kanamycin / Q000737:chemistry / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000201:enzymology / Q000235:genetics; D010802:Phylogeny; D016966:Porphyromonas gingivalis / Q000201:enzymology / Q000235:genetics; D021122:Protein Subunits; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D043262:Ribonuclease P; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000235:genetics
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D029968:Escherichia coli Proteins; D020035:Holoenzymes; D021122:Protein Subunits; C411972:R3G conjugate; D016337:RNA, Catalytic; C444521:neomycin B-arginine conjugate NeoR; D005601:Framycetin; D007612:Kanamycin; D001120:Arginine; D004722:Endoribonucleases; C468368:RPP14 protein, human; D043262:Ribonuclease P; C470865:ribonuclease P, E coli