Biology of N-methylpyrrole-N-methylimidazole hairpin polyamide.

Chemical substances that can recognize and bind DNA in a sequence-specific manner have enormous importance in modern biology and medicine. When covalently linked, hairpin polyamides made up of N-methylpyrrole (Py) and N-methylimidazole (Im) can bind to DNA in a sequence-specific manner. An Im opposite a Py recognizes and binds G:C from C:G, whereas a Py opposite an Im recognizes and binds to C:G. A Py-Py pair degenerately binds to T:A or A:T, whereas a hydroxypyrrole opposite a Py recognizes and binds to T:A from A:T, and vice versa. A variant in this recognition is the beta-alanine (beta-ala-beta-ala) pair, which also degenerately binds to A:T or T:A. The hairpin polyamides are cell permeable and bind to DNA at nanomolar concentrations, with binding coefficients similar to those of transcription factors. This review comprehensively discusses the current literature on using the sequence-specific recognition ability of the polyamides to study various DNA-protein interactions.

[1]  P. Dervan,et al.  Chemical approaches to control gene expression. , 2000, Gene expression.

[2]  M. Ptashne,et al.  Activation of gene expression by small molecule transcription factors. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Dervan,et al.  Selective inhibition of DNA gyrase in vitro by a GC specific eight‐ring hairpin polyamide at nanomolar concentration , 2000, FEBS letters.

[4]  S. John,et al.  Inhibition of human papilloma virus E2 DNA binding protein by covalently linked polyamides. , 2003, Nucleic acids research.

[5]  P. Dervan,et al.  Molecular recognition of DNA by small molecules. , 2001, Bioorganic & medicinal chemistry.

[6]  P. Dervan,et al.  Aliphatic/aromatic amino acid pairings for polyamide recognition in the minor groove of DNA , 1998 .

[7]  D. Baltimore,et al.  Inhibition of DNA Binding by NF-κB with Pyrrole-Imidazole Polyamides , 2002 .

[8]  K. Luger,et al.  Crystal structures of nucleosome core particles in complex with minor groove DNA-binding ligands. , 2003, Journal of molecular biology.

[9]  Heather C. Mefford,et al.  Use of fluorescent sequence-specific polyamides to discriminate human chromosomes by microscopy and flow cytometry , 2002, Nucleic Acids Res..

[10]  Peter B. Dervan,et al.  Regulation of gene expression by small molecules , 1997, Nature.

[11]  P. Dervan,et al.  Inhibition of Moloney murine leukemia virus integration using polyamides targeting the long-terminal repeat sequences. , 2003, Biochemistry.

[12]  J. Trauger,et al.  Importance of minor groove binding zinc fingers within the transcription factor IIIA-DNA complex. , 1997, Journal of molecular biology.

[13]  P. Dervan,et al.  The tax protein-DNA interaction is essential for HTLV-I transactivation in vitro. , 1999, Journal of molecular biology.

[14]  J. Trauger,et al.  Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  U. K. Laemmli,et al.  Specific targeting of insect and vertebrate telomeres with pyrrole and imidazole polyamides , 2001, The EMBO journal.

[16]  P. Dervan,et al.  Asymmetric DNA binding by a homodimeric bHLH protein. , 2000, Biochemistry.

[17]  J. Trauger,et al.  Minor groove DNA-protein contacts upstream of a tRNA gene detected with a synthetic DNA binding ligand. , 1999, Journal of molecular biology.

[18]  P. Dervan,et al.  Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids. , 2001, Organic letters.

[19]  C. Wang,et al.  Expanding the recognition of the minor groove of DNA by incorporation of beta-alanine in hairpin polyamides. , 2001, Bioorganic & medicinal chemistry.

[20]  P. Dervan,et al.  Promoter Scanning for Transcription Inhibition with DNA-Binding Polyamides , 2002, Molecular and Cellular Biology.

[21]  D C Rees,et al.  A structural basis for recognition of A.T and T.A base pairs in the minor groove of B-DNA. , 1998, Science.

[22]  P. Dervan,et al.  Inhibition of major groove DNA binding bZIP proteins by positive patch polyamides. , 2001, Bioorganic & medicinal chemistry.

[23]  Peter B. Dervan,et al.  Recognition of the four Watson–Crick base pairs in the DNA minor groove by synthetic ligands , 1998, Nature.

[24]  H. Sugiyama,et al.  Inhibition of transcription at a coding sequence by alkylating polyamide. , 2003, Journal of the American Chemical Society.

[25]  P. Dervan,et al.  Allosteric inhibition of protein--DNA complexes by polyamide--intercalator conjugates. , 2003, Journal of the American Chemical Society.

[26]  Jean-Louis Mergny,et al.  DNA duplex–quadruplex exchange as the basis for a nanomolecular machine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P. Dervan,et al.  Solid-phase synthesis of DNA binding polyamides on oxime resin. , 2002, Bioorganic & medicinal chemistry.

[28]  S. Penco,et al.  Structure and Synthesis of Distamycin A , 1964, Nature.

[29]  O. Cuvier,et al.  Specific gain- and loss-of-function phenotypes induced by satellite-specific DNA-binding drugs fed to Drosophila melanogaster. , 2000, Molecular cell.

[30]  C. Wang,et al.  Sequence-specific trapping of topoisomerase I by DNA binding polyamide-camptothecin conjugates. , 2001, Journal of the American Chemical Society.

[31]  J. Trauger,et al.  Anti-repression of RNA polymerase II transcription by pyrrole-imidazole polyamides. , 1999, Biochemistry.

[32]  P. Dervan,et al.  Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids , 1996 .

[33]  W. Fast.  Molecular radio jamming: autoinducer analogs. , 2003, Chemistry & biology.

[34]  E. Westhof,et al.  Four-way junctions in antisense RNA-mRNA complexes involved in plasmid replication control: a common theme? , 2001, Journal of molecular biology.

[35]  M. Ptashne,et al.  Towards a minimal motif for artificial transcriptional activators. , 2001, Chemistry & biology.

[36]  U. K. Laemmli,et al.  Chromatin opening of DNA satellites by targeted sequence-specific drugs. , 2000, Molecular cell.

[37]  P. Dervan,et al.  DNA crosslinking and biological activity of a hairpin polyamide-chlorambucil conjugate. , 2003, Nucleic acids research.

[38]  P. Dervan,et al.  Cellular uptake of N-methylpyrrole/N-methylimidazole polyamide-dye conjugates. , 2002, Bioorganic & medicinal chemistry.

[39]  P. Dervan,et al.  Sequence specific fluorescence detection of double strand DNA. , 2003, Journal of the American Chemical Society.

[40]  J. Trauger,et al.  Inhibition of Ets-1 DNA Binding and Ternary Complex Formation between Ets-1, NF-κB, and DNA by a Designed DNA-binding Ligand* , 1999, The Journal of Biological Chemistry.

[41]  C. Benz,et al.  Targeting the Ets Binding Site of the HER2/neuPromoter with Pyrrole-Imidazole Polyamides* , 2000, The Journal of Biological Chemistry.

[42]  D. Margolis,et al.  Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides , 2002, Journal of Virology.

[43]  M. Ptashne,et al.  Design of artificial transcriptional activators with rigid poly-L-proline linkers. , 2002, Journal of the American Chemical Society.

[44]  P. Dervan,et al.  Sequence specific alkylation of DNA by hairpin pyrrole-imidazole polyamide conjugates. , 2000, Chemistry & biology.

[45]  H. Sugiyama,et al.  Molecular design of a pyrrole-imidazole hairpin polyamides for effective DNA alkylation. , 2002, Chemistry.

[46]  Karolin Luger,et al.  Blocking transcription through a nucleosome with synthetic DNA ligands. , 2002, Journal of molecular biology.

[47]  P. Dervan,et al.  Inhibition of major-groove-binding proteins by pyrrole-imidazole polyamides with an Arg-Pro-Arg positive patch. , 1998, Chemistry & biology.

[48]  P. Dervan,et al.  Cell-free and Cellular Activities of a DNA Sequence Selective Hairpin Polyamide-CBI Conjugate* , 2002, The Journal of Biological Chemistry.