Neomycin B-cyclen conjugates and their Zn(II) complexes as RNA-binding agents

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Biochemistry

Background:

• Aminoglycoside antibiotics like neomycin B are crucial for treating bacterial infections.
• Understanding their interaction with ribosomal RNA is key to developing new therapeutic strategies.
• Modifying aminoglycoside structures can alter their binding properties and efficacy.

Purpose of the Study:

• To synthesize and characterize novel neomycin B-cyclen conjugates.
• To investigate the RNA-binding affinities of these conjugates and their metal complexes.
• To explore the potential of these modified aminoglycosides as new antimicrobial agents.

Main Methods:

• Synthesis of neomycin B-cyclen conjugates using peptide coupling protocols.
• Characterization via 1H NMR spectroscopy, mass spectrometry, and elemental analysis.
• FRET-based assays to measure binding affinity to prokaryotic ribosomal A-site RNA.

Main Results:

• Neomycin B-cyclen conjugates exhibited slightly higher binding affinities to ribosomal A-site RNA than neomycin B alone.
• Binding affinity increased with decreasing pH due to enhanced protonation of macrocyclic amines.
• Zinc(II) complexes of the conjugates demonstrated significantly higher affinities, indicating favorable interactions with RNA.

Conclusions:

• Covalent attachment of cyclen macrocycles and metal complexes can effectively tune the nucleic acid-binding properties of aminoglycosides.
• These modified aminoglycosides show promise for the development of novel antibacterial and antiviral therapies.
• The enhanced binding affinities suggest improved potential for therapeutic applications.