The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Otto Dahl - One of the best experts on this subject based on the ideXlab platform.
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Solid Phase Synthesis of oligodeoxynucleoside phosphorodithioates by a phosphotriester method using a chemoselective coupling reagent
Tetrahedron Letters, 1996Co-Authors: Jan Kehler, Ask Puschl, Otto DahlAbstract:Abstract A phosphotriester method has been developed for Solid Phase Synthesis of oligodeoxynucleoside phosphorodithioates. Couplings are performed by chemoselective oxygen activation of protected nucleoside dithiophosphate anions 1, 7, 8, 9 with 4-nitro-6-trifluoromethylbenzotriazol-1-yl-oxy-tris(pyrrolidine)-phosphonium hexafluorophosphate (PyFNOP). Under optimised conditions coupling yields are above 95% for 10 – 20 min couplings, and the products after deblocking are free from phosphorothioate contaminations (detection limit 0.5%).
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new Solid Phase Synthesis of oligodeoxythymidine phosphorodithioates by a modified hobt method
Tetrahedron Letters, 1995Co-Authors: Anne B. Eldrup, Jakob Felding, Jan Kehler, Otto DahlAbstract:Two new dithiophosphorylating reagents 2a,b have been prepared and shown to give nucleoside monomers 3a,b with reactivities suitable for Solid Phase Synthesis. An octamer and a nonamer deoxythymidine phosphorodithioate were prepared on a TentaGel support with good coupling efficiencies. The products after deblocking are free from phosphorothioate contaminations (detection limit 0.5%).
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Solid Phase Synthesis of oligodeoxyribonucleoside phosphorodithioates from thiophosphoramidites
Nucleic Acids Research, 1991Co-Authors: Kirsten Bjergarde, Otto DahlAbstract:Oligonucleoside phosphorodithioates 1 are modified DNA sequences with potential use as antisense oligonucleotides. The preparation of up to 20-mers containing all four bases by Solid Phase Synthesis is described, with details on the preparation of the four monomer units (protected nucleoside thiophosphoramidites 2), the conditions used for the assembly of the strands with up to 19 phosphorodithioate linkages, and the purification and characterisation of the products. Full-length homogeneity of HPLC-purified all-phosphorodithioate products is demonstrated by PAGE, but 31P NMR discloses the presence of phosphorothioate impurities (typically 8-9%), the origin of which is discussed. Oligonucleoside phosphorodithioates are freely soluble in water at neutral or basic pH, and are very stable towards oxidation, hydrolysis, and nuclease cleavage. Their ability to hybridize to complementary DNA has been studied by UV melting point (Tm) measurements. The observed depression of Tm, 0.5-2 degrees C per phosphorodithioate linkage, is higher that the 0.4-0.6 degrees C found for phosphorothioates.
Brian M. Paegel - One of the best experts on this subject based on the ideXlab platform.
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dna encoded Solid Phase Synthesis encoding language design and complex oligomer library Synthesis
ACS Combinatorial Science, 2015Co-Authors: Andrew B. Macconnell, Patrick J. Mcenaney, Valerie J. Cavett, Brian M. PaegelAbstract:The promise of exploiting combinatorial Synthesis for small molecule discovery remains unfulfilled due primarily to the “structure elucidation problem”: the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded Solid-Phase Synthesis (DESPS), comprising parallel compound Synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding position...
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DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis
2015Co-Authors: Andrew B. Macconnell, Patrick J. Mcenaney, Valerie J. Cavett, Brian M. PaegelAbstract:The promise of exploiting combinatorial Synthesis for small molecule discovery remains unfulfilled due primarily to the “structure elucidation problem”: the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded Solid-Phase Synthesis (DESPS), comprising parallel compound Synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length
Andrew B. Macconnell - One of the best experts on this subject based on the ideXlab platform.
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dna encoded Solid Phase Synthesis encoding language design and complex oligomer library Synthesis
ACS Combinatorial Science, 2015Co-Authors: Andrew B. Macconnell, Patrick J. Mcenaney, Valerie J. Cavett, Brian M. PaegelAbstract:The promise of exploiting combinatorial Synthesis for small molecule discovery remains unfulfilled due primarily to the “structure elucidation problem”: the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded Solid-Phase Synthesis (DESPS), comprising parallel compound Synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding position...
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DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis
2015Co-Authors: Andrew B. Macconnell, Patrick J. Mcenaney, Valerie J. Cavett, Brian M. PaegelAbstract:The promise of exploiting combinatorial Synthesis for small molecule discovery remains unfulfilled due primarily to the “structure elucidation problem”: the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded Solid-Phase Synthesis (DESPS), comprising parallel compound Synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length
Ute Schepers - One of the best experts on this subject based on the ideXlab platform.
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2 iminothiolane as a useful coupling reagent for polyamine Solid Phase Synthesis
Synlett, 2008Co-Authors: Frank Hahn, Klaus Mullen, Ute SchepersAbstract:Here, the versatility of 2-iminothiolane to act as coupling reagent for Solid-Phase Synthesis of polyamine conjugates is shown. This method, which supersedes the use of elaborate protection group strategies, allows the mild coupling of biomacromolecules and other functional moieties. Spermine conjugates with diverse maleimido building blocks were synthesized by a quick and selective reaction.
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Solid Phase Synthesis bioconjugation and toxicology of novel cationic oligopeptoids for cellular drug delivery
Bioconjugate Chemistry, 2007Co-Authors: Tina Schroder, Ute Schepers, Katja Schmitz, Nicole Niemeier, Teodor Silviu Balaban, Harald F Krug, Stefan BraseAbstract:For many therapeutic applications, it has become more and more important to find synthetic compounds that have the ability to transport a variety of drugs and cargo molecules into cells and tissues. Like arginine-rich cell-penetrating peptides (CPPs), it is already known that peptide mimetics such as β-peptides and peptoids can also express a transport function. In this study, ten fluorophore-labeled chiral and achiral peptoids with different backbone lengths and side chains as well as three peptoids coupled to a therapeutically active porphyrin moiety were prepared using a highly modular Solid-Phase Synthesis (SPP) approach. To compare the structural determinants with the cellular uptake efficiency, all peptoids were analyzed by live cell imaging. All cells show an even vesicular distribution of the internalized peptoids, also revealing that a vesicular escape into the cytosol was stronger for peptoids with longer backbones. Moreover, the uptake efficiency correlated with both the incubation time and the...
Jan Kehler - One of the best experts on this subject based on the ideXlab platform.
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Solid Phase Synthesis of oligodeoxynucleoside phosphorodithioates by a phosphotriester method using a chemoselective coupling reagent
Tetrahedron Letters, 1996Co-Authors: Jan Kehler, Ask Puschl, Otto DahlAbstract:Abstract A phosphotriester method has been developed for Solid Phase Synthesis of oligodeoxynucleoside phosphorodithioates. Couplings are performed by chemoselective oxygen activation of protected nucleoside dithiophosphate anions 1, 7, 8, 9 with 4-nitro-6-trifluoromethylbenzotriazol-1-yl-oxy-tris(pyrrolidine)-phosphonium hexafluorophosphate (PyFNOP). Under optimised conditions coupling yields are above 95% for 10 – 20 min couplings, and the products after deblocking are free from phosphorothioate contaminations (detection limit 0.5%).
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new Solid Phase Synthesis of oligodeoxythymidine phosphorodithioates by a modified hobt method
Tetrahedron Letters, 1995Co-Authors: Anne B. Eldrup, Jakob Felding, Jan Kehler, Otto DahlAbstract:Two new dithiophosphorylating reagents 2a,b have been prepared and shown to give nucleoside monomers 3a,b with reactivities suitable for Solid Phase Synthesis. An octamer and a nonamer deoxythymidine phosphorodithioate were prepared on a TentaGel support with good coupling efficiencies. The products after deblocking are free from phosphorothioate contaminations (detection limit 0.5%).