Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 Modifications at the C-terminus to improve pyrrole-imidazole polyamide activity in cell culture.

Literature DB >> 19572551

Modifications at the C-terminus to improve pyrrole-imidazole polyamide activity in cell culture.

Abstract

Pyrrole-imidazole (Py-Im) hairpin polyamides are a class of small molecule DNA minor groove binding compounds that have been shown to modulate endogenous gene expression in cell culture. Gene regulation by polyamides requires efficient cellular uptake and nuclear localization properties for candidate compounds. To further optimize Py-Im polyamides for enhanced potency in cell culture, a focused library of polyamides possessing various modifications at the C-terminus was synthesized and tested. Comparison of polyamide biological activity in two cell lines revealed tolerance for structural modifications and agreement in activity trends between cell lines. The use of an oxime linkage between the polyamide and an aromatic functionality on the C-terminus resulted in a approximately 20-fold increase in the potency of polyamides targeted to the androgen response element (ARE) in LNCaP cells by measuring AR-activated PSA expression.

Entities: CellLine Chemical Disease Gene Species

Mesh：

Substances：

Year: 2009 PMID： 19572551 PMCID： PMC2788682 DOI： 10.1021/jm900256f

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

23 in total

1. Cellular uptake of N-methylpyrrole/N-methylimidazole polyamide-dye conjugates.

Authors: Jason M Belitsky; Stephanie J Leslie; Paramjit S Arora; Terry A Beerman; Peter B Dervan
Journal: Bioorg Med Chem Date: 2002-10 Impact factor: 3.641

2. DMSO-related effects in protein characterization.

Authors: Agneta Tjernberg; Natalia Markova; William J Griffiths; Dan Hallén
Journal: J Biomol Screen Date: 2006-02-20

3. Hydrolytic stability of hydrazones and oximes.

Authors: Jeet Kalia; Ronald T Raines
Journal: Angew Chem Int Ed Engl Date: 2008 Impact factor: 15.336

4. Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands.

Authors: S White; J W Szewczyk; J M Turner; E E Baird; P B Dervan
Journal: Nature Date: 1998-01-29 Impact factor: 49.962

5. Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.

Authors: Bogdan Z Olenyuk; Guo-Jun Zhang; Jeffery M Klco; Nicholas G Nickols; William G Kaelin; Peter B Dervan
Journal: Proc Natl Acad Sci U S A Date: 2004-11-19 Impact factor: 11.205

6. Completion of a Programmable DNA-Binding Small Molecule Library.

Authors: Carey F Hsu; John W Phillips; John W Trauger; Michelle E Farkas; Jason M Belitsky; Alexander Heckel; Bogdan Z Olenyuk; James W Puckett; Clay C C Wang; Peter B Dervan
Journal: Tetrahedron Date: 2007-07-02 Impact factor: 2.457

7. Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamide.

Authors: Nicholas G Nickols; Peter B Dervan
Journal: Proc Natl Acad Sci U S A Date: 2007-06-12 Impact factor: 11.205

8. Solid-phase synthesis of DNA binding polyamides on oxime resin.

Authors: J M Belitsky; D H Nguyen; N R Wurtz; Peter B Dervan
Journal: Bioorg Med Chem Date: 2002-08 Impact factor: 3.641

9. Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface.

Authors: Nicholas G Nickols; Claire S Jacobs; Michelle E Farkas; Peter B Dervan
Journal: ACS Chem Biol Date: 2007-08-17 Impact factor: 5.100

10. In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography.

Authors: Daniel A Harki; Nagichettiar Satyamurthy; David B Stout; Michael E Phelps; Peter B Dervan
Journal: Proc Natl Acad Sci U S A Date: 2008-08-27 Impact factor: 11.205

12 in total

1. Inhibition of heat shock transcription factor binding by a linear polyamide binding in an unusual 1:1 mode.

Authors: Rongsheng E Wang; Raj K Pandita; Jianfeng Cai; Clayton R Hunt; John-Stephen Taylor
Journal: Chembiochem Date: 2011-12-01 Impact factor: 3.164

Review 2. Small-molecule regulators that mimic transcription factors.

Authors: José A Rodríguez-Martínez; Kimberly J Peterson-Kaufman; Aseem Z Ansari
Journal: Biochim Biophys Acta Date: 2010-09-06

3. Modulation of topoisomerase IIα expression and chemosensitivity through targeted inhibition of NF-Y:DNA binding by a diamino p-anisyl-benzimidazole (Hx) polyamide.

Authors: Luke Pett; Konstantinos Kiakos; Vijay Satam; Pravin Patil; Sarah Laughlin-Toth; Matthew Gregory; Michael Bowerman; Kevin Olson; Mia Savagian; Megan Lee; Moses Lee; W David Wilson; Daniel Hochhauser; John A Hartley
Journal: Biochim Biophys Acta Gene Regul Mech Date: 2016-10-24 Impact factor: 4.490

Modifications at the C-terminus to improve pyrrole-imidazole polyamide activity in cell culture.

1. Cellular uptake of N-methylpyrrole/N-methylimidazole polyamide-dye conjugates.

2. DMSO-related effects in protein characterization.

3. Hydrolytic stability of hydrazones and oximes.

4. Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands.

5. Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.

6. Completion of a Programmable DNA-Binding Small Molecule Library.

7. Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamide.

8. Solid-phase synthesis of DNA binding polyamides on oxime resin.

9. Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface.

10. In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography.

1. Inhibition of heat shock transcription factor binding by a linear polyamide binding in an unusual 1:1 mode.

Review 2. Small-molecule regulators that mimic transcription factors.

3. Modulation of topoisomerase IIα expression and chemosensitivity through targeted inhibition of NF-Y:DNA binding by a diamino p-anisyl-benzimidazole (Hx) polyamide.

Review 4. Programmable DNA-binding small molecules.

Review 5. Structure-based DNA-targeting strategies with small molecule ligands for drug discovery.

6. Enhancing the cellular uptake of Py-Im polyamides through next-generation aryl turns.

7. Characterization and solubilization of pyrrole-imidazole polyamide aggregates.

Review 8. Fluorescent probes for nucleic Acid visualization in fixed and live cells.

9. Single-dose pharmacokinetic and toxicity analysis of pyrrole-imidazole polyamides in mice.

10. Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides.