Send to

Choose Destination
See comment in PubMed Commons below
Chem Biol. 2006 Sep;13(9):993-1000.

Synthesis and testing of a focused phenothiazine library for binding to HIV-1 TAR RNA.

Author information

  • 1Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.


We have synthesized a series of phenothiazine derivatives, which were used to test the structure-activity relationship of binding to HIV-1 TAR RNA. Variations from our initial compound, 2-acetylphenothiazine, focused on two moieties: ring substitutions and n-alkyl substitutions. Binding characteristics were ascertained via NMR, principally by saturation transfer difference spectra of the ligand and imino proton resonance shifts of the RNA. Both ring and alkyl substitutions manifested NMR changes upon binding. In general, the active site, while somewhat flexible, has regions that can be capitalized for increased binding through van der Waals interactions and others that can be optimized for solubility in subsequent stages of development. However, binding can be nontrivially enhanced several-fold through optimization of van der Waals and hydrophilic sites of the scaffold.

[PubMed - indexed for MEDLINE]
Free full text

LinkOut - more resources

Full Text Sources

Other Literature Sources

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk