Surface plasmon resonance evaluation of various aminoglycoside-RNA hairpin interactions reveals low degree of selectivity

被引:40
作者
Verhelst, SHL
Michiels, PJA
van der Marel, GA
van Boeckel, CAA
van Boom, JH
机构
[1] Leiden Univ, Leiden Inst Chem, Gorlaeus Labs, NL-2300 RA Leiden, Netherlands
[2] NV Organon, Lead Discovery Unit, NL-5340 BH Oss, Netherlands
关键词
aminoglycosides; antibiotics; RNA recognition; surface plasmon resonance;
D O I
10.1002/cbic.200300819
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aminoglycoside antibiotics, which are able to selectively bind to RNA, are considered to be an important lead in RNA-targeting drug discovery. In this study, surface plasmon resonance (SPR) was employed to explore the interaction of aminoglycosides with known tobramycin-binding RNA hairpins (aptamers) and an unrelated RNA hairpin, It was established that aminoglycosides have multiple interactions with RNA hairpins. Unexpectedly, the different hairpins showed comparable affinity for a set of related aminoglycosides. The observed absence of selectivity presents on extra hurdle in the discovery of novel aminoglycosides as specific drugs that target defined RNA hairpins.
引用
收藏
页码:937 / 942
页数:6
相关论文
共 37 条
  • [1] Probing the specificity of aminoglycoside ribosomal RNA interactions with designed synthetic analogs
    Alper, PB
    Hendrix, M
    Sears, P
    Wong, CH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (09) : 1965 - 1978
  • [2] The binding site of a specific aminoglycoside binding RNA molecule
    Cho, JY
    Hamasaki, K
    Rando, RR
    [J]. BIOCHEMISTRY, 1998, 37 (14) : 4985 - 4992
  • [3] NEOMYCIN INHIBITION OF THE HAMMERHEAD RIBOZYME INVOLVES IONIC INTERACTIONS
    CLOUETDORVAL, B
    STAGE, TK
    UHLENBECK, OC
    [J]. BIOCHEMISTRY, 1995, 34 (35) : 11186 - 11190
  • [4] Targeting RNA with small-molecule drugs: Therapeutic promise and chemical challenges
    Gallego, J
    Varani, G
    [J]. ACCOUNTS OF CHEMICAL RESEARCH, 2001, 34 (10) : 836 - 843
  • [5] Minimal RNA constructs that specifically bind aminoglycoside antibiotics with high affinities
    Hamasaki, K
    Killian, J
    Cho, JY
    Rando, RR
    [J]. BIOCHEMISTRY, 1998, 37 (02) : 656 - 663
  • [6] Direct observation of aminoglycoside-RNA interactions by surface plasmon resonance
    Hendrix, M
    Priestley, ES
    Joyce, GF
    Wong, CH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (16) : 3641 - 3648
  • [7] Hermann T, 2000, ANGEW CHEM INT EDIT, V39, P1891
  • [8] HERMANN T, 2000, ANGEW CHEM, V112, P1962
  • [9] STRUCTURAL FEATURES THAT GIVE RISE TO THE UNUSUAL STABILITY OF RNA HAIRPINS CONTAINING GNRA LOOPS
    HEUS, HA
    PARDI, A
    [J]. SCIENCE, 1991, 253 (5016) : 191 - 194
  • [10] JAEGER W, 2000, CARBOHYDRATES CHEM 1, V2, P1045