The Pattern of Distribution of Amino Groups Modulates the Structure and Dynamics of Natural Aminoglycosides: Implications for RNA Recognition

  1. Corzana, F. 23
  2. Cuesta, I. 3
  3. Freire, F. 3
  4. Revuelta, J. 3
  5. Torrado, M. 3
  6. Bastida, A. 3
  7. Jiménez-Barbero, J. 1
  8. Asensio, J.L. 3
  1. 1 Centro de Investigaciones Biológicas

    Centro de Investigaciones Biológicas

    Madrid, España


  2. 2 Universidad de La Rioja

    Universidad de La Rioja

    Logroño, España


  3. 3 Instituto de Química Orgánica General

    Instituto de Química Orgánica General

    Madrid, España


Journal of the American Chemical Society

ISSN: 0002-7863

Datum der Publikation: 2007

Ausgabe: 129

Nummer: 10

Seiten: 2849-2865

Art: Artikel

DOI: 10.1021/JA066348X PMID: 17298063 SCOPUS: 2-s2.0-33947197265 GOOGLE SCHOLAR

Andere Publikationen in: Journal of the American Chemical Society


Aminoglycosides are clinically relevant antibiotics that participate in a large variety of molecular recognition processes involving different RNA and protein receptors. The 3-D structures of these policationic oligosaccharides play a key role in RNA binding and therefore determine their biological activity. Herein, we show that the particular NH 2/NH 3 +/OH distribution within the antibiotic scaffold modulates the oligosaccharide conformation and flexibility. In particular, those polar groups flanking the glycosidic linkages have a significant influence on the antibiotic structure. A careful NMR/theoretical analysis of different natural aminoglycosides, their fragments, and synthetic derivatives proves that both hydrogen bonding and charge-charge repulsive interactions are at the origin of this effect. Current strategies to obtain new aminoglycoside derivatives are mainly focused on the optimization of the direct ligand/receptor contacts. Our results strongly suggest that the particular location of the NH 2/NH 3 +/OH groups within the antibiotics can also modulate their RNA binding properties by affecting the conformational preferences and inherent flexibility of these drugs. This fact should also be carefully considered in the design of new antibiotics with improved activity. © 2007 American Chemical Society.