A Convenient Method for the Synthesis of DNA-Recognizing Polyamides in Solution

Xiao, Junhua; Yuan, Gu; Huang, Wenqiu; Chan, AS; Lee, Kam-Len Daniel

doi:10.1021/jo000135n

Cited by 59 publications

(45 citation statements)

References 42 publications

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“…[19] Perylene derivative Tel01 (2) was synthesized by refluxing a mixture of 3,4,9,10-perylenetetracarboxylic dianhydride and 3-(dimethylamino)propylamine (Dp) (yield 86 %).…”

Section: Methodsmentioning

confidence: 99%

“…Tel01 contains a huge aromatic system in favor of p stacking with G-quartets. [16][17][18][19] Results and Discussion Formation of the G-quadruplexes: Firstly, we chose 15 6-nt oligonucleotides with different sequences and studied the formation of the G-quadruplexes (Table 1). The ESI-MS spectra revealed only three G-quadruplex peaks associated with these sequences; dA (Figure 2), indicating that formation of a parallel tetramer quadruplex requires at least four continuous guanines in the 6-nt sequence.…”

Section: Introductionmentioning

confidence: 99%

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Formation and Stability of G‐Quadruplexes Self‐Assembled from Guanine‐Rich Strands

Zhou

Yuan

Liu

et al. 2007

Chemistry A European J

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Electrospray ionization mass spectrometry (ESI-MS) was utilized to investigate the formation and stability of G-quadruplexes. For the 15 6-nt oligonucleotides tested, ESI-MS indicated that formation of a parallel tetramer quadruplex requires at least four continuous guanines in the 6-nt sequence. In addition, the G-rich strands prefer to employ "self-association" in the formation of the G-quadruplex rather than hybridized integration, and the thermodynamic-stability order of these three G-quadruplexes is Q(2)>Q(1)>Q(3).

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“…[19] Perylene derivative Tel01 (2) was synthesized by refluxing a mixture of 3,4,9,10-perylenetetracarboxylic dianhydride and 3-(dimethylamino)propylamine (Dp) (yield 86 %).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formation and Stability of G‐Quadruplexes Self‐Assembled from Guanine‐Rich Strands

Zhou

Yuan

Liu

et al. 2007

Chemistry A European J

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“…18) Direct coupling of b-alanine with pyrrole monomer Nmethyl-4-nitro-2-trichloroacetylpyrrole 1 without any coupling reagent generated monomer derivative 4 and 5, from which dimeric pyrrole amide 6 and 8 were prepared, respectively. These two dimers were among the key building blocks in the present synthesis.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Cellular Effect of a Novel Conjugate of Polyamide and Phospholipid

Liu

Deng

Zheng

et al. 2006

CHEMICAL & PHARMACEUTICAL BULLETIN

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Small molecules with the ability to target predetermined sequences of DNA would be valuable tools in molecular biology and potentially in human medicine.1-3) Synthetic polyamides consisting of N-methylpyrrole (Py) and Nmethylimidazole (Im) have received special attention due to their high DNA affinity, sequence specificity, and relatively small size. [4][5][6] These polyamides have been shown to interfere with protein-DNA interactions, and have the potential to modulate gene expression by designing to recognize specific DNA sequences. 5) For polyamides to be effective in gene regulation, they must reach their target DNA inside the cell. 5,7)However, there are few examples and only circumstantial evidence that suggest that polyamides bind to nuclear DNA targets in living eukaryotic cells. [7][8][9][10][11][12] In the present studies, we designed a conjugate in which a phosphatidylcholine (PC) was attached to the polyamide. The introduction of the phospholipid was expected to improve the permeability of the synthetic molecule through the cell membrane, guide the movement toward to nucleus in cells, and thereby reduce the cytotoxicity. The phospholipid is a primary component of biologicall membrane, and has proven to be noncytotoxic. In particular, the hydrophobic tail of the lipid is possible to greatly benefit the movement of the conjugate toward to nucleus in cells, and subsequently promote the interaction with nucleic DNA. 13) Results and DiscussionPolyamide 10 (O 2 N-PyPy-b-PyPy-b-OEt) and the targeted conjugate 13 (O 2 N-PyPy-b-PyPy-b-PC) were synthesized as shown in Chart 1. b-Alanine (b) functioned as a spacer both in polyamide 10 and conjugate 13. 10 is a regular structure among the synthetic polyamides.14,15) Based on the DNAbinding study results of natural product distamycin and netropsin 16,17) and the pairing rules of polyamides binding to DNA derived by Dervan 14) the polyamide 10 and the polyamide moiety in the designed conjugate 13 were presumed to have an ability of DNA-binding in A/T and T/A pairs rich region.Primarily, DCC coupling method was used in the synthesis.18) Direct coupling of b-alanine with pyrrole monomer Nmethyl-4-nitro-2-trichloroacetylpyrrole 1 without any coupling reagent generated monomer derivative 4 and 5, from which dimeric pyrrole amide 6 and 8 were prepared, respectively. These two dimers were among the key building blocks in the present synthesis. In the preliminary experiment of tetrameric amide synthesis, coupling of acid 7 of the dimer with the amino dimer generated from the hydrogenation of 6 was presumed to give the methyl ester of the tetrameric amide, which would be the desired polyamide and would also serve as another key building block for the conjugate. However, hydrogenation of the nitro group of 6 by the catalysis of palladium on carbon formed many side-products rather than the desired one detected by TLC method. While ethyl ester 8, instead of 6, prepared by the same method as that for the preparation of 6 was used in the reaction the desired reduction product...

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“…[22] The perylene derivative Tel01 was synthesized by the refluxed mixture of 3,4,9,10-perylenetetracarboxylic dianhydride and 3-(dimethylamino)propylamine (Dp) (yield 86 %).…”

Section: Methodsmentioning

confidence: 99%

“…Keywords: circular dichroism · DNA recognition · human telomeres · mass spectrometry · quadruplexes role; Im = N-methylimidazole; g = g-aminobutyric acid; b = b-alanine; Dp = N,N-dimethylpropyldiamine), which have good cell permeation and binding preference on base G, [21,22] and a perylene derivate (Tel01), containing a conjugate aromatic system in favor of p stacking with G-quartets. [23] Results and Discussion…”

Section: Introductionmentioning

confidence: 99%

Specific Recognition of Human Telomeric G‐Quadruplex DNA with Small Molecules and the Conformational Analysis by ESI Mass Spectrometry and Circular Dichroism Spectropolarimetry

Zhou¹,

Yuan²

2007

Chemistry A European J

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Electrospray ionization mass spectrometry (ESI-MS) was utilized to investigate the binding affinity and stoichiometry of small molecules with human telomeric G-quadruplex DNA. The binding-affinity order obtained for the (AGGGTT)(4) quadruplex was: Tel01>ImImImbetaDp>>PyPyPygammaImImImbetaDp. The specific binding of Tel01 and PyPyPygammaImImImbetaDp in one system consisting of human telomeric G-quadruplex and duplex DNA was observed directly for the first time. This revealed that PyPyPygammaImImImbetaDp has a binding specificity for the duplex DNA, whereas Tel01 selectively recognizes the G-quadruplex DNA. Moreover, both ESI-MS and circular dichroism (CD) spectra indicated that Tel01 favored the formation and stabilization of the antiparallel G-quadruplex, and a structural transition of the (AGGGTT)(4) sequence from a coexistence of parallel and antiparallel G-quadruplexes to a parallel G-quadruplex induced by annealing.

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A Convenient Method for the Synthesis of DNA-Recognizing Polyamides in Solution

Cited by 59 publications

References 42 publications

Formation and Stability of G‐Quadruplexes Self‐Assembled from Guanine‐Rich Strands

Formation and Stability of G‐Quadruplexes Self‐Assembled from Guanine‐Rich Strands

Synthesis and Cellular Effect of a Novel Conjugate of Polyamide and Phospholipid

Specific Recognition of Human Telomeric G‐Quadruplex DNA with Small Molecules and the Conformational Analysis by ESI Mass Spectrometry and Circular Dichroism Spectropolarimetry

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