- 4-Methyltrityl-Protected Pyrrole and Imidazole Building Blocks for Solid Phase Synthesis of DNA-Binding Polyamides
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DNA-binding polyamides are synthetic oligomers of pyrrole/imidazole units with high specificity and affinity for double-stranded DNA. To increase their synthetic diversity, we report a mild methodology based on 4-methyltrityl (Mtt) solid phase peptide synthesis (SPPS), whose building blocks are more accessible than the standard Fmoc and Boc SPPS ones. We demonstrate the robustness of the approach by preparing and studying a hairpin with all precursors. Importantly, our strategy is orthogonal and compatible with sensitive molecules and could be readily automated.
- Heinrich, Benedikt,Vázquez, Olalla
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supporting information
p. 533 - 536
(2020/01/31)
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- NOVEL BENZODIAZEPINE DERIVATIVES
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The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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Page/Page column 141-142
(2010/08/18)
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- SEQUENCE SELECTIVE PYRROLE AND IMIDAZOLE POLYAMIDE METALLOCOMPLEXES
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The present invention relates to sequence selective compounds for targeting therapeutic or diagnostic groups to polynucleotides. More particularly, the present invention relates to sequence selective targeting of metallocomplexes, such as metallodrugs and metallodiagnostics, to polynucleotides.
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Page/Page column 54
(2010/02/11)
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- Synthesis of N-methylpyrrole and N-methylimidazole amino acids suitable for solid-phase synthesis
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New and higher yielding synthetic routes to N-protected N-methylpyrrole and N-methylimidazole amino acids are introduced to circumvent difficulties associated with established schemes. Key steps in each synthesis include copper-mediated cross-coupling reaction to directly install a carbamate-protected 4-amine in the N-methylpyrrole derivative and effective nitration followed by a one-pot reduction/Boc protection of the amine in the synthesis of the N-Me-imidazole amino acid.
- Jaramillo, David,Liu, Qi,Aldrich-Wright, Janice,Tor, Yitzhak
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p. 8151 - 8153
(2007/10/03)
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- Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids
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Matrix presented Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of many naturally occurring DNA binding proteins. A machine-assisted Fmoc solid phase synthesis of polyamides has been optimized to afford high stepwise coupling yields (>99%). Two monomer building blocks, Fmoc-Py acid and Fmoc-Im acid, were prepared in multigram scale. Cleavage by aminolysis followed by HPLC purification affords up to 200 mg quantities of polyamide with purities and yields greater than or equal to those reported using Boc chemistry. A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available peptide synthesizers.
- Wurtz, Nicholas R.,Turner, James M.,Baird, Eldon E.,Dervan, Peter B.
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p. 1201 - 1203
(2007/10/03)
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- Method for the synthesis of pyrrole and imidazole carboxamides on a solid support
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The present invention describes a novel method for the solid phase synthesis of polyamides containing imidazole and pyrrole carboxamides. The polyamides are prepared on a solid support from aromatic carboxylic acids and aromatic amines with high stepwise coupling yields (>99%), providing milligram quantities of highly pure polyamides. The present invention also describes the synthesis of analogs of the natural products Netropsin and Distamycin A, two antiviral antibiotics. The present invention also describes a novel method for the solid phase synthesis of imidazole and pyrrole carboxamide polyamide-oligonucleotide conjugates. This methodology will greatly increase both the complexity and quantity of minor-groove binding polyamides and minor-groove binding polyamide-oligonucleotide conjugates which can be synthesized and tested.
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- Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids
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The solid phase synthesis of sequence specific DNA binding polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids is described. Two monomer building blocks, Boc-Py-OBt ester and Boc-Im acid, are prepared on a 50 g scale without column chromatography. Using commercially available Boc-β-alanine-Pam resin, cycling protocols were optimized to afford high stepwise coupling yields (>99%). Deprotection by aminolysis affords up to 100 mg quantities of polyamide. Solid phase methodology increases both the number and complexity of minor groove binding polyamides which can be synthesized and analyzed with regard to DNA binding affinity and sequence specificity. The solid phase synthesis of a representative eight-residue polyamide is reported.
- Baird, Eldon E.,Dervan, Peter B.
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p. 6141 - 6146
(2007/10/03)
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- The Preparation and Properties of Partially Protected 4-Amino-1-methylimidazole-2-carboxylic Acids to be Used as Intermediates in the Synthesis of Analogues of Distamycin A
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Partially protected 4-amino-1-methylimidazole-2-carboxylic acid derivatives have been prepared by a convenient route from the corresponding nitro analogue.Such derivatives, blocked on the amino function with tert-butyloxycarbonyl (4) or formyl groups (8)
- Grehn, Leif,Ding, Lu,Ragnarsson, Ulf
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