PMID: 9545429Apr 18, 1998Paper

Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with an Arg-Pro-Arg positive patch

Chemistry & Biology
R E BremerP B Dervan

Abstract

Gene-specific targeting of any protein-DNA complex by small molecules is a challenging goal at the interface of chemistry and biology. Polyamides containing N-methylimidazole and N-methylpyrrole amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to many naturally occurring DNA-binding proteins. It has been shown that an eight-ring hairpin polyamide targeted to a specific minor-groove contact within a transcription factor binding site can inhibit protein-DNA binding and gene transcription. Polyamides and certain major-groove-binding proteins have been found to co-occupy the DNA helix, however. To expand the number of genes that can be targeted by pyrrole/imidazole polyamides, we set out to develop a class of polyamides that can selectively inhibit major-groove-binding proteins. An eight-ring hairpin polyamide conjugated to a carboxy-terminal Arg-Pro-Arg tripeptide was designed to deliver a positive residue to the DNA backbone and interfere with protein-phosphate contacts. Gel mobility shift analysis demonstrated that a polyamide hairpin-Arg-Pro-Arg binding in the minor groove selectively inhibits binding of the transcription factor GCN4 (222-281) in the adjacent major groove. Substitution ...Continue Reading

References

Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·Y W Park, K J Breslauer
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M MrksichP B Dervan
Jan 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G Duval-ValentinC Hélène
May 1, 1990·Electrophoresis·R F JohnstonD L Barker
Aug 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J G Pelton, D E Wemmer
Oct 12, 1987·Nucleic Acids Research·B L Iverson, P B Dervan
Jan 1, 1980·Methods in Enzymology·A M Maxam, W Gilbert
Mar 1, 1994·Nature Structural Biology·X ChenM Sundaralingam
Sep 27, 1994·Proceedings of the National Academy of Sciences of the United States of America·S N HoG R Crabtree
Jan 1, 1994·Annual Review of Biochemistry·W J GehringT Bürglin
Dec 16, 1994·Science·J K Strauss, L J Maher
Jul 29, 1994·Cell·W J GehringK Wüthrich
Oct 7, 1993·Nature·Y KimP B Sigler
Jan 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·C LiuP K Vogt
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·D S PilchP B Dervan
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·S Y ChiangT A Beerman
May 8, 1997·Nature·J M GottesfeldP B Dervan
Jan 7, 1998·Journal of Molecular Biology·L NeelyJ M Gottesfeld
Feb 14, 1998·Nature Structural Biology·C L KielkopfD C Rees

❮ Previous
Next ❯

Citations

Nov 26, 2002·Biochemical Pharmacology·Jason L LarabeeJay S Hanas
Jul 2, 2003·Current Opinion in Structural Biology·Peter B Dervan, Benjamin S Edelson
Dec 22, 1999·Current Opinion in Chemical Biology·P B Dervan, R W Bürli
Apr 22, 2008·ACS Chemical Biology·Rocco MorettiAseem Z Ansari
Feb 13, 2003·Nucleic Acids Research·Thomas D SchaalBhavin S Parekh
Apr 2, 2004·Biological & Pharmaceutical Bulletin·Musti Sree Rama Chandra Murty, Hiroshi Sugiyama
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·A Tutter, K A Jones
Aug 4, 2004·Journal of Biotechnology·Christian MelanderJoel M Gottesfeld
Jun 19, 2001·Chemistry & Biology·A Z AnsariM Ptashne
Feb 27, 1999·Journal of Molecular Biology·S J McBryantJ M Gottesfeld
Sep 26, 2000·Bioorganic & Medicinal Chemistry·A L Satz, T C Bruice
Apr 6, 2002·Bioorganic & Medicinal Chemistry Letters·Daniela FattoriAntonello Pessi
May 7, 2002·Nature Reviews. Cancer·Laurence H Hurley
Dec 3, 2011·Chembiochem : a European Journal of Chemical Biology·Rongsheng E WangJohn-Stephen Taylor
Jun 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mélanie LambertMarie-Hélène David-Cordonnier
Feb 18, 2012·Chemistry : a European Journal·Wenbin HuThomas Schrader
Dec 16, 2003·Chemical Society Reviews·M Eugenio VázquezJ L Mascareñas
Jun 9, 2001·Journal of Molecular Biology·J M GottesfeldP B Dervan
Dec 28, 1999·Bioorganic & Medicinal Chemistry Letters·A L Satz, T C Bruice
Jul 8, 1998·Chemistry & Biology·C Denison, T Kodadek
Mar 20, 2003·Journal of the American Chemical Society·Toshikazu BandoHiroshi Sugiyama
Jul 10, 2003·Journal of the American Chemical Society·Eric J Fechter, Peter B Dervan
Jul 22, 2004·Journal of the American Chemical Society·Toshikazu BandoHiroshi Sugiyama

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.