S J Sucheck | PubMed Health

PubMed2001

Combinatorial synthesis of aminoglycoside libraries.

The interaction of aminoglycosides with RNA represents a paradigm in the use of small molecules as effectors of RNA function. Aminoglycosides bind and affect the function of a variety of therapeutically useful RNA targets and show antimicrobial as well as antiviral activities. However, due to the complex nature of aminoglycosides, efforts for synthesizing large libraries of these structures to screen against prospective biological targets have been limited. This review covers the recent advances in the generation of aminoglycoside libraries.

Aminoglycosides↗

PubMed2000

RNA as a target for small molecules.

Proteins are folded to form a small binding site for catalysis or ligand recognition and this small binding site is traditionally the target for drug discovery. An alternative target for potential drug candidates is the translational process, which requires a precise reading of the entire mRNA sequence and, therefore, can be interrupted with small molecules that bind to mRNA sequence-specifically. RNA thus presents itself as a new upstream target for drug discovery because of the critical role it plays in the life of pathogens and in the progression of diseases. In this post-genomic era, RNA is becoming increasingly amenable to small-molecule therapy as greater structural and functional information accumulates with regard to important RNA functional domains. The study of aminoglycoside antibiotics and their binding to 16S ribosomal RNA has been a paradigm for our understanding of the ways in which small molecules can be developed to affect the function of RNA.

Base Sequence↗