A small molecule transcriptional activation domain.
Artificial transcriptional activators are excellent tools for studying the mechanistic details of transcriptional regulation. Furthermore, as the correlation between a wide range of human diseases and misregulated transcription becomes increasingly evident, such molecules may in the long run serve as the basis for transcription-based therapeutic agents. The greatest challenge in this arena has been the discovery of organic molecules that are functional mimics of transcriptional activation domains, sequences of natural proteins that participate in a variety of protein-protein interactions to control transcriptional levels. We describe the first examples of small molecules that function in this capacity, isoxazolidines containing an array of polar and hydrophobic functional groups. Despite their small size, the most potent of the structures functions nearly as well as a natural activation domain.
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Aaron R
AR
Minter
Brian B
BB
Brennan
Anna K
AK
Mapp
D051696:Activating Transcription Factors; D001665:Binding Sites; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry* / Q000502:physiology*; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D015533:Transcriptional Activation
D051696:Activating Transcription Factors; D001798:Blood Proteins; D007555:Isoxazoles; D010446:Peptide Fragments; D014157:Transcription Factors