Helmut Rosemeyer | University of Osnabrück (original) (raw)

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Papers by Helmut Rosemeyer

Research paper thumbnail of Cleavage of DNA without loss of genetic information by incorporation of a disaccharide nucleoside

Nucleic acids research, 2003

A ribose residue inserted between the 3'-OH of one nucleotide and the 5'-phosphate group ... more A ribose residue inserted between the 3'-OH of one nucleotide and the 5'-phosphate group of the next nucleotide, functions as a site-specific cleavage site within DNA. This extra ribose does not interrupt helix formation and it protects duplex DNA against cleavage by restriction enzymes. Cleavage can be obtained with periodate and all ribose fragments can be removed with sodium hydroxide. As a result of this, an intact natural oligodeoxynucleotide is obtained after ligation reaction, which means that site-specific cleavage and recovering of intact DNA occurs without loss of genetic information.

Research paper thumbnail of Isomeric N-methyl-7-deazaguanines: synthesis, structural assignment, and inhibitory activity on xanthine oxidase

Journal of Medicinal Chemistry, 1984

The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synth... more The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.

Research paper thumbnail of Analysis of Phenacylester Derivatives of Fatty Acids from Human Skin Surface Sebum by Reversed-Phase HPLC: Chromatographic Mobility as a Function of Physico-Chemical Properties

International Journal of Molecular Sciences, 2007

A set of 13 fatty acids was transformed into their phenacyl esters by reaction with phenacyl brom... more A set of 13 fatty acids was transformed into their phenacyl esters by reaction with phenacyl bromide in acetonitrile using 18-crown-6 as phase-transfer catalyst. Conditions for the RP-18 HPL chromatographic separation of most of the esters has been worked out. Using this standard the fatty acid spectra from skin surface sebum lipids of 17 test persons was taken after microwave-assisted hydrolysis, neutralization and extraction with n-hexane. Quantitative evaluation of the chromatograms exhibits that oleic acid predominates in the sebum of all test persons. In the second part of the work the chromatographic mobility (R E values) of fatty acid phenacyl esters is correlated with calculated physico-chemical parameters of the corresponding acids. The best linear correlation was found between the R E and the logP values. This is helpful for the structural elucidation of un-identified fatty acids in a chromatogram.

Research paper thumbnail of The alpha-D anomer of 5-aza-7-deaza-2'-deoxyguanosine

Acta Crystallographica Section C Crystal Structure Communications

In the monohydrate of 2-amino-8-(2-deoxy-alpha-D-erythro-pentofuranosyl)-8H-imidazo[1,2-a][1,3,5]... more In the monohydrate of 2-amino-8-(2-deoxy-alpha-D-erythro-pentofuranosyl)-8H-imidazo[1,2-a][1,3,5]triazin-4-one, C(10)H(13)N(5)O(4) x H(2)O, denoted (I) or alpha Z(d), the conformation of the N-glycosylic bond is in the high-anti range [chi = 87.5 (3)]. The 2'-deoxyribofuranose moiety adopts a C2'-endo,C3'-exo((2')T(3')) sugar puckering (S-type sugar) and the conformation at the C4'-C5' bond is -sc (trans).

Research paper thumbnail of Nucleolipids as Potential Organogelators

Research paper thumbnail of Fluoreszierende Ethenonucleoside und Oligonucleotide mit hoher Stabilität

Research paper thumbnail of 1,N6-Etheno-7-deaza-2'-deoxyadenosine - A Stable and Highly Fluorescent Analogue of Ethenoadenosine: Synthesis, Properties and Oligonucleotide Incorporation

Research paper thumbnail of 7-Carbapurine Ribofuranosides: Synthesis by Solid-Liquid Phase-Transfer Glycosylation and 15 N-NMR Spectra

Nucleosides and Nucleotides, 1988

ABSTRACT

Research paper thumbnail of Nucleolipids of 5-Fluorouridine: Synthesis, Acidic Stability, Lipophilicity, and Neurobiological Activity

Research paper thumbnail of ChemInform Abstract: 1-(2′-Deoxy-β-D-xylofuranosyl)cytosine: Base Pairing of Oligonucleotides with a Configurationally Altered Sugar-Phosphate Backbone

Research paper thumbnail of Nucleolipids and Use Thereof and Devices for Nucleic Acid Analysis

Research paper thumbnail of Solid-phase synthesis of oligo(2'-deoxyxylonucleotides) and PCR amplification of base-modified DNA fragments

Nucleic Acids Symposium Series

1-(2'-Deoxy-beta-D-threo-pentofuranosyl)thymine (xTd) and -adenine (xAd) were converted i... more 1-(2'-Deoxy-beta-D-threo-pentofuranosyl)thymine (xTd) and -adenine (xAd) were converted into their appropriately protected 3'-phosphonates 1a, 2a as well as their 2-cyanoethyl phosphoramidites 1b, 2b. These compounds were used for solid-phase syntheses of the oligo(2'-deoxy-beta-D-xylonucleotides) 5-8. Structural properties and behavior against nucleases is described. Apart from oligo(2'-deoxyxylonucleotides) the PCR-amplification of a pUC18 DNA fragment with Taq polymerase was studied in the presence of the 7-deazapurine derivatives of dGTP, dATP, and dITP. The incorporation efficiency of the modified compounds was compared with those of the parent nucleotides. 7-Deaza-2'-deoxyguanosine protected the DNA-fragment from hydrolysis by the restriction endodeoxyribonuclease Eco RI, Pst I, Bam HI, and Sma I if the nucleoside was located within the recognition site.

Research paper thumbnail of Nucleolipids: Synthesis of Pro- and Co-Drugs and their Biological Activity

The search for new or improved pharmaceuticals for the treatment of illnesses imposes high demand... more The search for new or improved pharmaceuticals for the treatment of illnesses imposes high demands on nearly all scientific disciplines. This results from a lacking efficacy of the drug and from the toxicity of the substances. The treatment of malignant tumors requires a medication addressing intracellular targets. The cytostatic chemical therapy belongs to the molecular targeted therapy forms with so-called small molecules (M w ≤ 800g/mol). For these hydrophilic compounds, however, the lipophilic cell membrane is a barrier. This leads to low bioavailability and short biological half-life times for the so-called Active Pharmaceutical Ingredients (APis).

Research paper thumbnail of Colloid-Bonded Medicinal Compounds

The invention relates to colloids bound medicinal compounds or fluorescent markers, to a process ... more The invention relates to colloids bound medicinal compounds or fluorescent markers, to a process for the preparation thereof, and to a pharmaceutical formulation containing such compounds.

Research paper thumbnail of 5-Fluorouracil Derivatives

The present invention relates to 5-fluorouracil derivatives represented by formula I, pharmaceuti... more The present invention relates to 5-fluorouracil derivatives represented by formula I, pharmaceutical compositions comprising said derivatives and their use in the treatment of cancer as well as a process for prepairing the 5-fluorouracil derivatives represented by formula I.

Research paper thumbnail of Building Blocks for the Synthesis of Oligonucleotides with Hydrophobic Internucleotide Linkages

Research paper thumbnail of logP-Values of Nucleosides and Nucleolipids

Nucleolipids are abbreviated by NL. The first number (green) refers to the nucleoside. The second... more Nucleolipids are abbreviated by NL. The first number (green) refers to the nucleoside. The second number (blue) refers to the moiety at the 2',3'-position at the glyconic ring; cyclic moieties are abbreviated by "cycl" before the number.. The third number (pink) refers to the lipophilic moiety at the base [N(3) for pyrimidines]. The fourth number (orange) refers to a lipophilic moiety at the 5'-O-position. Identical residues carry the same number; "0" stands for a molecule without a residue at this position.

Research paper thumbnail of 2-Azapurine Compounds and Their Uses

Within oligonucleotides 2-azapurine and especially 2-azaadenine bases form specifically base pair... more Within oligonucleotides 2-azapurine and especially 2-azaadenine bases form specifically base pairs with guanine. This base pair is of analogous stability as an adenine-thymine but less stable than a guanine-cytosine base pair. Therefore, the incorporation of 2-azaadenine residues into oligonucleotides instead of cytosine leads specifically to hybridization complexes with nucleic acids with homogenous stability. This is useful for the adaptation of the stabilities of different oligonucleotide sequences in all kinds of hybridization techniques, for example in oligomer chip technology.

Research paper thumbnail of Incorporation of lipophilic nucleic acid single strands with different nucleolipid head groups into an artificial lipid bilayer

The video presents a new bilayer technique used for the insertion and immobilization of Cy-5 - la... more The video presents a new bilayer technique used for the insertion and immobilization of Cy-5 - labelled lipo oligonucleotides (LONs) into artificial lipid membranes. The structure and lipophilicity of the nucleolipid head group is varied. https://repositorium.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2014091012807 For referring to this source please use the identification number: urn:nbn:de:gbv:700-2014091012807

Research paper thumbnail of Reactive, lipophilic nucleoside building blocks for the synthesis of hydrophobic nucleic acids

The present invention relates to a method for the isolation and/or identification of known or unk... more The present invention relates to a method for the isolation and/or identification of known or unknown sequences of nucleic acids (target sequences) optionally marked with reporter groups by base specific hybridisation with, essentially, complementary sequences (in the following referred to as sample oligonucleotides, sample sequences or sample nucleic acids), which belong to a library of sequences. Further, the invention relates to nucleolipids used in the method of the invention and a process for the preparation of said nucleolipids. In addition, the invention refers to a pharmaceutical composition comprising said nucleolipids.

Research paper thumbnail of Cleavage of DNA without loss of genetic information by incorporation of a disaccharide nucleoside

Nucleic acids research, 2003

A ribose residue inserted between the 3'-OH of one nucleotide and the 5'-phosphate group ... more A ribose residue inserted between the 3'-OH of one nucleotide and the 5'-phosphate group of the next nucleotide, functions as a site-specific cleavage site within DNA. This extra ribose does not interrupt helix formation and it protects duplex DNA against cleavage by restriction enzymes. Cleavage can be obtained with periodate and all ribose fragments can be removed with sodium hydroxide. As a result of this, an intact natural oligodeoxynucleotide is obtained after ligation reaction, which means that site-specific cleavage and recovering of intact DNA occurs without loss of genetic information.

Research paper thumbnail of Isomeric N-methyl-7-deazaguanines: synthesis, structural assignment, and inhibitory activity on xanthine oxidase

Journal of Medicinal Chemistry, 1984

The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synth... more The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.

Research paper thumbnail of Analysis of Phenacylester Derivatives of Fatty Acids from Human Skin Surface Sebum by Reversed-Phase HPLC: Chromatographic Mobility as a Function of Physico-Chemical Properties

International Journal of Molecular Sciences, 2007

A set of 13 fatty acids was transformed into their phenacyl esters by reaction with phenacyl brom... more A set of 13 fatty acids was transformed into their phenacyl esters by reaction with phenacyl bromide in acetonitrile using 18-crown-6 as phase-transfer catalyst. Conditions for the RP-18 HPL chromatographic separation of most of the esters has been worked out. Using this standard the fatty acid spectra from skin surface sebum lipids of 17 test persons was taken after microwave-assisted hydrolysis, neutralization and extraction with n-hexane. Quantitative evaluation of the chromatograms exhibits that oleic acid predominates in the sebum of all test persons. In the second part of the work the chromatographic mobility (R E values) of fatty acid phenacyl esters is correlated with calculated physico-chemical parameters of the corresponding acids. The best linear correlation was found between the R E and the logP values. This is helpful for the structural elucidation of un-identified fatty acids in a chromatogram.

Research paper thumbnail of The alpha-D anomer of 5-aza-7-deaza-2'-deoxyguanosine

Acta Crystallographica Section C Crystal Structure Communications

In the monohydrate of 2-amino-8-(2-deoxy-alpha-D-erythro-pentofuranosyl)-8H-imidazo[1,2-a][1,3,5]... more In the monohydrate of 2-amino-8-(2-deoxy-alpha-D-erythro-pentofuranosyl)-8H-imidazo[1,2-a][1,3,5]triazin-4-one, C(10)H(13)N(5)O(4) x H(2)O, denoted (I) or alpha Z(d), the conformation of the N-glycosylic bond is in the high-anti range [chi = 87.5 (3)]. The 2'-deoxyribofuranose moiety adopts a C2'-endo,C3'-exo((2')T(3')) sugar puckering (S-type sugar) and the conformation at the C4'-C5' bond is -sc (trans).

Research paper thumbnail of Nucleolipids as Potential Organogelators

Research paper thumbnail of Fluoreszierende Ethenonucleoside und Oligonucleotide mit hoher Stabilität

Research paper thumbnail of 1,N6-Etheno-7-deaza-2'-deoxyadenosine - A Stable and Highly Fluorescent Analogue of Ethenoadenosine: Synthesis, Properties and Oligonucleotide Incorporation

Research paper thumbnail of 7-Carbapurine Ribofuranosides: Synthesis by Solid-Liquid Phase-Transfer Glycosylation and 15 N-NMR Spectra

Nucleosides and Nucleotides, 1988

ABSTRACT

Research paper thumbnail of Nucleolipids of 5-Fluorouridine: Synthesis, Acidic Stability, Lipophilicity, and Neurobiological Activity

Research paper thumbnail of ChemInform Abstract: 1-(2′-Deoxy-β-D-xylofuranosyl)cytosine: Base Pairing of Oligonucleotides with a Configurationally Altered Sugar-Phosphate Backbone

Research paper thumbnail of Nucleolipids and Use Thereof and Devices for Nucleic Acid Analysis

Research paper thumbnail of Solid-phase synthesis of oligo(2'-deoxyxylonucleotides) and PCR amplification of base-modified DNA fragments

Nucleic Acids Symposium Series

1-(2'-Deoxy-beta-D-threo-pentofuranosyl)thymine (xTd) and -adenine (xAd) were converted i... more 1-(2'-Deoxy-beta-D-threo-pentofuranosyl)thymine (xTd) and -adenine (xAd) were converted into their appropriately protected 3'-phosphonates 1a, 2a as well as their 2-cyanoethyl phosphoramidites 1b, 2b. These compounds were used for solid-phase syntheses of the oligo(2'-deoxy-beta-D-xylonucleotides) 5-8. Structural properties and behavior against nucleases is described. Apart from oligo(2'-deoxyxylonucleotides) the PCR-amplification of a pUC18 DNA fragment with Taq polymerase was studied in the presence of the 7-deazapurine derivatives of dGTP, dATP, and dITP. The incorporation efficiency of the modified compounds was compared with those of the parent nucleotides. 7-Deaza-2'-deoxyguanosine protected the DNA-fragment from hydrolysis by the restriction endodeoxyribonuclease Eco RI, Pst I, Bam HI, and Sma I if the nucleoside was located within the recognition site.

Research paper thumbnail of Nucleolipids: Synthesis of Pro- and Co-Drugs and their Biological Activity

The search for new or improved pharmaceuticals for the treatment of illnesses imposes high demand... more The search for new or improved pharmaceuticals for the treatment of illnesses imposes high demands on nearly all scientific disciplines. This results from a lacking efficacy of the drug and from the toxicity of the substances. The treatment of malignant tumors requires a medication addressing intracellular targets. The cytostatic chemical therapy belongs to the molecular targeted therapy forms with so-called small molecules (M w ≤ 800g/mol). For these hydrophilic compounds, however, the lipophilic cell membrane is a barrier. This leads to low bioavailability and short biological half-life times for the so-called Active Pharmaceutical Ingredients (APis).

Research paper thumbnail of Colloid-Bonded Medicinal Compounds

The invention relates to colloids bound medicinal compounds or fluorescent markers, to a process ... more The invention relates to colloids bound medicinal compounds or fluorescent markers, to a process for the preparation thereof, and to a pharmaceutical formulation containing such compounds.

Research paper thumbnail of 5-Fluorouracil Derivatives

The present invention relates to 5-fluorouracil derivatives represented by formula I, pharmaceuti... more The present invention relates to 5-fluorouracil derivatives represented by formula I, pharmaceutical compositions comprising said derivatives and their use in the treatment of cancer as well as a process for prepairing the 5-fluorouracil derivatives represented by formula I.

Research paper thumbnail of Building Blocks for the Synthesis of Oligonucleotides with Hydrophobic Internucleotide Linkages

Research paper thumbnail of logP-Values of Nucleosides and Nucleolipids

Nucleolipids are abbreviated by NL. The first number (green) refers to the nucleoside. The second... more Nucleolipids are abbreviated by NL. The first number (green) refers to the nucleoside. The second number (blue) refers to the moiety at the 2',3'-position at the glyconic ring; cyclic moieties are abbreviated by "cycl" before the number.. The third number (pink) refers to the lipophilic moiety at the base [N(3) for pyrimidines]. The fourth number (orange) refers to a lipophilic moiety at the 5'-O-position. Identical residues carry the same number; "0" stands for a molecule without a residue at this position.

Research paper thumbnail of 2-Azapurine Compounds and Their Uses

Within oligonucleotides 2-azapurine and especially 2-azaadenine bases form specifically base pair... more Within oligonucleotides 2-azapurine and especially 2-azaadenine bases form specifically base pairs with guanine. This base pair is of analogous stability as an adenine-thymine but less stable than a guanine-cytosine base pair. Therefore, the incorporation of 2-azaadenine residues into oligonucleotides instead of cytosine leads specifically to hybridization complexes with nucleic acids with homogenous stability. This is useful for the adaptation of the stabilities of different oligonucleotide sequences in all kinds of hybridization techniques, for example in oligomer chip technology.

Research paper thumbnail of Incorporation of lipophilic nucleic acid single strands with different nucleolipid head groups into an artificial lipid bilayer

The video presents a new bilayer technique used for the insertion and immobilization of Cy-5 - la... more The video presents a new bilayer technique used for the insertion and immobilization of Cy-5 - labelled lipo oligonucleotides (LONs) into artificial lipid membranes. The structure and lipophilicity of the nucleolipid head group is varied. https://repositorium.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2014091012807 For referring to this source please use the identification number: urn:nbn:de:gbv:700-2014091012807

Research paper thumbnail of Reactive, lipophilic nucleoside building blocks for the synthesis of hydrophobic nucleic acids

The present invention relates to a method for the isolation and/or identification of known or unk... more The present invention relates to a method for the isolation and/or identification of known or unknown sequences of nucleic acids (target sequences) optionally marked with reporter groups by base specific hybridisation with, essentially, complementary sequences (in the following referred to as sample oligonucleotides, sample sequences or sample nucleic acids), which belong to a library of sequences. Further, the invention relates to nucleolipids used in the method of the invention and a process for the preparation of said nucleolipids. In addition, the invention refers to a pharmaceutical composition comprising said nucleolipids.