Biomedical subjects
Publications and source records attributed to F Seela.
The 9-deazaguanine N7-2'-deoxyribofuranoside (3) as well as the bromo and iodo derivatives 4a,b were synthesized and incorporated in oligonucleotide duplexes and triplexes. Their base pairing properties were investigated and compared with those of the parent purine N7-2'-deoxyribofuanosides.
The phosphoramidites of 8-aza-7-deaza-2'-deoxyisoguanosine (1a) and its bromo derivative 1b as well as of 6-aza-2'-deoxyisocytidine and its 5-methyl derivative (3a,b) were synthesized. Parallel-stranded duplexes containing the nucleosides 1a,b show a significantly enhanced duplex stability compared to those containing 2'-deoxyisoguanosine.
The synthesis of phosphoramidites containing 7-deazaguanine, 7-deazaadenine, uracil and cytosine carrying aminopropargyl chains is described. The corresponding oligonucleotides are stabilized in duplexes thermally as well as against degradation by exonucleases.
The pyrazolo[3,4-d]pyrimidine-4,6-diamine nucleosides 2b-d stabilize the dA-dT base pair significantly when the dA-residue is replaced. Oligonucleotide duplexes incorporating 2b-d show a 4-6 degrees C Tm increase per modification. The 7-bromo compound 2b harmonizes the stability of the dA-dT vs. the dG-dC pair. According to this the stability of such duplexes depends no longer on the base pair composition of a DNA molecule.
Self-complementary [[5'-d(G-C)4]2] and non-selfcomplementary oligonucleotides [5'-d(TAG GTC AAT ACT) x 3'-d(ATC CAG TTA TGA)] containing 7-(omega-aminoalkyn-1-yl)-7-deaza-2'-deoxyguanosines (1a-c) (1) and 7-deaza-2'-deoxyguanosine instead of dG were studied regarding their thermal stability as well as their phosphodiester hydrolysis by either 3' --> 5'- or 5' --> 3'-phosphodiesterase studied by MALDI-TOF MS.
The H-phosphonate and the phosphoramidite of N7-2'-deoxyisoguanosine (2) were prepared and incorporated into oligonucleotide duplexes. Their base pairing properties were investigated and compared with those of the parent purine nucleosides.
The 7-bromo- (4a) and 7-iodo- (4b) derivatives of 7-deaza-2'-deoxyxanthosine (5) are prepared. Furthermore, the building blocks 6-8 of 7-deaza-2'-deoxyxanthosine (5) are synthesized and tested for their usage in oligonucleotide synthesis.
A biospecific resin for the retardation of ribosomal peptodyltransferase by affinity chromatography was prepared by condensing the alpha-amino group of puromycin with the N-hydroxysuccinimide ester of CH-Sepharose 4B to yield the resin-linked puromycin derivative 4.
The preparation of a new photochemically-activatable polymer was accomplished by condensation of aminohexyl-6-yl-agarose with the N-hydroxysuccinimide ester of 5-azido-2-nitro-benzoic acid. The latter compound was obtained by diazotization of 5-amino-2-nitro-benzoic acid, exchange of the diazonium group through azide and condensation with N-hydroxysuccinimide. As shown for the photolysis on the monomer level, irradiation of the polymer led to the intermediate formation of a highly reactive nitrene, which is able to immobilize ligands e. g. L-phenylalanine to the polymer.
The photochemically activatable heterobifunctional reagent 5-azido-3-nitro-omega-bromo-acetophenone (3) was synthesized by condensation of 3,5-dinitrobenzoyl chloride with diethyl malonate, acid-catalyzed decarboxylation of the formed malonester derivative 1 to 3,5-dinitro-acetophenone (2a), selective reduction of one nitro group in 2a to 5-amino-3-nitro-acetophenone (2b) and diazotization to 2c. Nucleophilic displacement of the diazonium group in 2c by sodium azide forms 5-azido-3-nitro-acetophenone (2d) which gives 3 after bromination. Compound 3 is photochemically labile and forms an highly reactive nitrene during ultraviolet irradiation. Since compound 3 is able to alkylate amino- or mercapto-groups of amino acids or nucleosides via its bromoacetyl residue, the bifunctional reagent 3 should cross link proteins or nucleic acids after nitrene generation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.