Specific inhibition of formation of transcription complexes by a calicheamicin oligosaccharide: A paradigm for the development of transcriptional antagonists Journal Article
| Authors: | Ho, S. N.; Boyer, S. H.; Schreiber, S. L.; Danishefsky, S. J.; Crabtree, G. R. |
| Article Title: | Specific inhibition of formation of transcription complexes by a calicheamicin oligosaccharide: A paradigm for the development of transcriptional antagonists |
| Abstract: | Sequence-specific DNA ligands that antagonize DNA-protein interactions represent a potentially powerful means of modulating gene expression. Calicheamicin γ1(I), a member of the DNA-cleaving enediyne class of anticancer antibiotics, binds to specific DNA sequences through an aryltetrasaccharide domain. To take advantage of this unique sequence- specific recognition capability, the methyl glycoside of the aryltetrasaccharide of calicheamicin γ1(I) (CLM-MG) was used to investigate the ability of glycoconjugate DNA ligands to inhibit DNA-protein interactions. CLM-MG inhibits the formation of DNA-protein complexes at micromolar concentrations in a sequence-specific manner and rapidly dissociates preformed complexes. CLM-MG also inhibits transcription in vivo with similar sequence specificity. These results suggest a strategy for the development of a class of novel biological probes and therapeutic agents. |
| Keywords: | controlled study; dose response; transcription factor; drug structure; hela cell; drug synthesis; gene expression regulation; transcription regulation; genetic transfection; reporter gene; dna sequence; dna binding; antineoplastic antibiotic; dissociation; dna cleavage; leukemia cell line; protein dna interaction; oligosaccharide; glycoconjugate; glycoside; dna protein complex; priority journal; article; calicheamicin gamma1; calicheamicin derivative |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 91 |
| Issue: | 20 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1994-09-27 |
| Start Page: | 9203 |
| End Page: | 9207 |
| Language: | English |
| DOI: | 10.1073/pnas.91.20.9203 |
| PROVIDER: | scopus |
| PMCID: | PMC44780 |
| PUBMED: | 7937742 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: PNASA C2 -- Source: Scopus |
