A convenient method for the synthesis of DNA-recognizing polyamides in solution

A convenient method for the synthesis of polyamides containing N-methylpyrrole (Py) and N-methylimidazole (Im) in solution has been developed. Most of the building blocks have been prepared by a haloform reaction in a simple way that column chromatography can be avoided. By use of the DCC/HOBT coupling reaction, the building blocks prepared have been effectively connected to construct a variety of subchains and polyamides without employing amino protection and deprotection. By use of the present method, an eight-ring polyamide, PyPyPyPygammaPyImImPybetaDp (gamma is gamma-aminobutyric acid, beta is beta-alanine, Dp is N, N-dimethylpropyldiamine), has been synthesized by the coupling of two four-ring subchains in one step.     

N-甲基吡咯类聚酰胺的合成及其与DNA的相互作用

本研究主要是设计并合成了3个含有4个N-甲基吡咯的聚酰胺化合物(PyPyPyPyβDp,PyPyPyPyγDp, NO₂PyPyPyPyβDp),并使用ESI-MS法研究了其与DNA的相互作用.     

Protonation and Alkylation of Cross-conjugated Ketones Containing a Terminal N-Methylpyrrole Ring

The protonation and alkylation of cross-conjugated ketones containing a terminal N-methylpyrrole ring takes place at the oxygen atom. Protonation is accompanied by a strong bathochromic shift of the absorption maximum in the electron spectrum, while alkylation leads to ethoxypolymethine salts. The possibility of using these salts for the synthesis of ethoxycyanine dyes was studied.     

Synthesis of Pyrrole-Imidazole Polyamide

Small molecules that target specific predetermined DNA sequences have the potential tocontrol gene expression'. Realization of the high affinity binding and specific recognitionof DNA sequences by organic molecules is one of the focuses of biological chemistry.The natural products netropsin and distamycin are N-methylpyrrole containing di- andtripeptides, with binding specificity at sites of successive A.T or T.A base pairs of DNAin the minor groove'. Recently, N-methylimidazole is intro…     

Synthesis of polyamide containing pyrrole and imidazole amino acids

A polyainide containing N-methylpyrrole ( Py) and N-methylimidazole (Im) amino acids was synthesized by coupling two of the four-ring oligopeptide chains using DCC/ HOBT as promoting additives. The structure of the polyamide was confirmed by 1R, NMR and MS spectra.     

Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids

[structure: see text]. 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.     

Expanding the repertoire of natural product-inspired ring pairs for molecular recognition of DNA

A furan amino acid, inspired by the recently discovered proximicin natural products, was incorporated into the scaffold of a DNA-binding hairpin polyamide. While unpaired oligomers of 2,4-disubstituted furan amino acids show poor DNA-binding activity, furan (Fn) carboxamides paired with N-methylpyrrole (Py) and N-methylimidazole (Im) rings demonstrate excellent stabilization of duplex DNA as well as discrimination of noncognate sequences, consistent with function as a Py mimic according to the Py/Im polyamide pairing rules.     

Amino-catalyzed fragmentation characteristics of polyamides containing N-methylpyrrole and N-methylimidazole by electrospray negative ionization mass spectrometry

Different negative fragmentations of synthesized polyamides containing N-methylpyrrole and N-methylimidazole were analyzed by electrospray ionization tandem mass spectrometry with low-energy collision-induced dissociation. An interesting rearrangement derived from amino catalysis of N-methylimidazole was observed. The observation is useful for the study of the correlations between the sequences of polyamides and their mass fragmentation pathways.     

脂肪链在吡咯-咪唑聚酰胺及其结合物与B-DNA键合中的作用

吡咯-咪唑聚酰胺是一类人工合成的能够在B-DNA小沟特异性识别碱基序列的有机小分子,并且能通过细胞膜进入细胞,调控基因的表达。它主要由五元杂环化合物N-甲基吡咯(Py)、N-甲基咪唑(Im)、N-甲基-3-羟基吡咯(Hp)芳香氨基酸及脂肪链氨基酸组成。在这种小分子对生物大分子识别事件中, 脂肪链^作为构建聚酰胺及其结合物的一部分, 在聚酰胺特异性识别DNA、延长DNA识别序列、连接分子荧光标记、对DNA指定位点的烷基化及基因调控等方面都起着非常重要的作用。本文阐述了脂肪链在上述诸方面应用的研究进展,并简要地分析了存在的问题和应用前景。     

特异性识别DNA的吡咯-咪唑多聚酰胺的研究进展

吡咯-咪唑多聚酰胺为一类人工合成的主要由五元杂环化合物N-甲基吡咯(Py)、N-甲基咪唑(Im)和N-甲基3-羟基吡咯(Hp)芳香氨基酸组成的,经酰胺键连接的人工小分子配体.它们具有与天然DNA结合蛋白相媲美的DNA特异性识别和结合能力.近20年来,对此类化合物的研究取得了重要进展,确定了简单的氨基酸对识别碱基对的规则,研究了多种方式连接的吡咯-咪唑多聚酰胺与DNA小沟结合模式,合成了多种双功能吡咯-咪唑多聚酰胺,且吡咯-咪唑多聚酰胺能穿过细胞膜,具有在体内外调节基因表达的作用。     

Synthesis and antimicrobial activity of some netropsin analogues

Nine novel lexitropsins were synthesized by linking two netropsin-like moieties through three different dicarboxylic acids; 9,10-dihydro-2,7-phenanthrenedicarboxylic acid; [(3-[[(carboxymethyl)amino]carbonyl]benzoyl)amino]acetic acid and indole-2,5-dicarboxylic acid. The netropsin residues were modified by the use of N-isopentylpyrrole, 5-methylthiophene or 5-isopropylthiazole heterocyclic building blocks in place of the usual N-methylpyrrole. The compounds were tested against five gram-positive bacteria: Staphylococcus aureus, Streptomyces faecalis, methicillin resistant Staphylococcus aureus, Enterobacter cloacae, Mycobacterium fortuitum, three gram-negative bacteria: Klebsiella aerogenes, Proteus vulgaris, Escherichia coli and three fungi: Aspergillus niger, Candida albicans and Aspergillus nidulans. Some of the compounds showed significant inhibitory effects on the growth of the microorganisms.     

Synthesis of directly linked diazine isosteres of pyrrole-polyamide that photochemically cleave DNA

A distamycin model containing an isosteric diazine linked pyrrole has been designed and synthesized. The key steps of the synthesis involved the successful diazotization of the 4-amino-pyrrole derivatives to give the diazomium salts, which undergo coupling reactions with N-methylpyrrole to yield the directly linked diazine compounds. The amide isosteric-diazine pyrrole I demonstrated photo-induced DNA damage upon iradiation with UV light (365 nm). Spectrophotometric and mass spectrometric identification suggest that the azo-linkage in I did not dissociate during irradiation. Moreover, compound I produced DNase I footprints with the HexB DNA fragment at AT sites, as well as some other mixed sequences (5'-ATGTCG-3'), indicative of the additional role of the diazine-linkage for interaction at the duplex DNA.     

Electrospray Ionization Mass Spectral Characteristics of Polyamide Containing 1,4,7,10-Tetraazacyclododecane

The study of the fragmentations of the protonated molecular species[M H]~ and selected fragment ions al-lowed proposals for the main fragmentation pathways of the title compound.In order to better understand the frag-mentation pathways,the MS~3 and MS~4 spectra of the title compound were obtained.The main fragmentation path-ways occur by the cleavage of the C-CO bonds between N-methylpyrrole and carbonyl groups,CO-NH amidebonds,NH-C bonds between the NH groups and the N-methylpyrrole rings,and N-C bonds in1,4,7,10-tetraazacyclododecane.Electrospray ionization was proven to be a good method for the structural charac-terization and identification of this kind of compound.     

A new colorimetric chemodosimeter for Hg2+ based on charge-transfer compound of N-methylpyrrole with TCNQ

Reaction of N-methylpyrrole and 7,7,8,8-tetracyanoquinodimethane (TCNQ) furnishes an intense blue unsymmetrical charge-transfer compound through regioselective attachment of tricyanoquinodimethane at the 2-position of N-methylpyrrole which was found to be selective chemodosimeter for Hg²⁺ ions in CH₃CN:H₂O mixture (1:1 v/v, pH = 7.0, 0.01 M HEPES, 0.15 M NaCl) as well as in the solid state when supported on silica, over a variety of metal ions. A plausible mechanism for the sensing process has been proposed and supported through the characterization of the resulting Hg²⁺ complex and the density functional theory (DFT) studies.     

Substitution in a number of five-membered heterocycles with one heteroatom catalytic alkylation of N-methylpyrrole and thiophene with olefins

It has been found that a decrease in the yield of -substituted products during alkylation with olefins is observed in a number of five-membered heterocycles (furan, thiophene, and N-methylpyrrole). The change in the -orienting effect depends not only on the nature of the heteroatom but also on the type of reaction and on the conditions of the process. In the case of N-methylpyrrole, the possibility of C-alkylation of the pyrrole ring with olefins was demonstrated for the first time.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 502–506, April, 1973.     

Electrospray ionization tandem mass spectrometric characteristics and fragmentation mechanisms of distamycin analogues

The electrospray ionization tandem mass spectrometric (ESI-MS/MS) characteristics and fragmentation mechanisms of eight distamycin analogues containing N-methylpyrrole and N-methylimidazole were investigated. The members of two isomeric groups of distamycin analogues with the same elemental composition can be distinguished by MS/MS spectra of protonated molecules and of significant fragment ions.     

Synthesis of a Pair of Derivatives of N-Methylpyrrole Polyamide

A pair of derivatives of tetrameric N-methylpyrrole polyamide were synthesized in order to develop a new method for the study of interaction of the polyamide derivatives with DNA. Indole acetic acid and nicotinic acid were introduced to the polyamide in the synthesized compound, which showed an expected red shift in the UV spectrum. These compounds may function as a potential tool in the detection of the polyamide binding to DNA.     

Influence of surface morphology on the colloidal and electronic behavior of conjugated polymer-silica microspheres

A template approach to the synthesis of a series of conjugated polymer-mesoporous silica composite microspheres is described. Poly(3,4-ethylenedioxythiophene) (PEDOT), poly(thiophene), and poly( N-methylpyrrole) composites were prepared. The surface morphology of the samples was analyzed by scanning electron microscopy, and it was found that well-defined, monodisperse colloidal materials could only be prepared when the monomer is insoluble in the polymerization medium. The filling of the mesopores was systematically varied from 0% to 100%, and powder X-ray diffraction and nitrogen adsorption studies were used to confirm the pore filling. Thermogravimetric analysis shows that the polymer loading tracks the monomer loading in an asymptotic fashion. Conductivity measurements show that the conductivity of the PEDOT materials is relatively constant at high polymer loadings but decreases exponentially at low loadings. Measurements of the electrophoretic mobility were made in order to explain this behavior. These data suggest that, at high polymer loadings, the particle surface is characteristic of the polymer, while at low polymer loadings it is characteristic of the silica host. These results identify important design criteria for the template synthesis of a variety of new colloidal materials. Importantly, these optimized parameters may open the door to the preparation of colloids and colloidal crystals of previously unprocessable materials.     

C-Phosphorylation of Electron-Rich Heterocycles by Trivalent Phosphorus Halides

Abstract

Convenient methods for introducing dihalogenphosphinogroup at of pyrrole and hran rings have been developed. It was found that dibromphosphinogroup migrated from the second to the third position of the N-methylpyrrole. Convenient methods for phosphorylation of N- alkylcarbazole and iminostilbene have been developed.