Search PubMed⌕ Search

Biomedical subjects

L Beigelman

Publications and source records attributed to L Beigelman.

41 records · Page 3Linked to original sources
PubMed1995

Synthesis and biological activities of a phosphorodithioate analog of 2',5'-oligoadenylate.

To enhance the resistance of 2-5A (pppA2'p5'A2'p5'A) to degradation by exo- and endonucleases, a phosphorodithioate analog was synthesized using a solid-phase phosphite triester approach with N6-benzoyl-5'-O-dimethoxytrityl-3'-O-t-butyldimethylsilyladenosine 2'-[S-(beta-thiobenzoylethyl)-pyrrolidinophosphorothioamidit e]. 5'-Monophosphorylation was accomplished with 2-[2-(4,4'-dimethoxytrityloxy)-ethylsulfonyl]ethyl-(2-cyanoe thyl)-(N,N- diisopropyl)-phosphoramidite. The resulting product, p5'A2'(s2p)- 5'A2'(s2p)5'A, was approximately 10-fold less effective as an activator of purified human recombinant 2-5A-dependent RNase than was 2-5A itself. This loss of activation ability was related directly to the loss of binding ability of the phosphorodiothioate analog. As predicted, p5'A2'(s2p)5'A2' (s2p)5'A was stable to snake venom phosphodiesterase and the nucleolytic activities of both human lymphoblastoid CEM cell extracts and human serum, under conditions that led to facile degradation of parent 2-5A. This nuclease stability permitted the observation of the CEM cell extracts and human serum phosphatase activity which led to 5'-dephosphorylation of p5'A2'(s2p)5'A2'(s2p)5'A.

Adenine Nucleotides↗
PubMed1994

The 2,6-diaminopurine riboside.5-methylisocytidine wobble base pair: an isoenergetic substitution for the study of G.U pairs in RNA.

Phylogenetically invariant G.U wobble pairs are present in a wide variety of RNA's. As a means to study the contribution of individual chemical groups within a G.U pair, we have synthesized and thermodynamically characterized oligoribonucleotides containing the unnatural nucleosides 2,6-diaminopurine riboside (DAP) and 5-methylisocytidine (MeiC). The DAP.MeiC pair at the end of an RNA duplex is as stable as a G.U pair, consistent with formation of a wobble base pair with two hydrogen bonds. DAP.MeiC is a valuable substitution for the study of G.U wobble pairs because it is conformationally similar to the G.U pair, but has a different array of functional groups in the major and minor grooves of the duplex and a reversed hydrogen bonding polarity between the bases. We also report the stability of several other terminal pairs proposed to be in a wobble configuration including inosine.U (I.U), A.MeiC, DAP.C, A.C, G.5-methyl-U,2'-deoxyguanosine.U, and 2'-deoxy-7-deazaguanosine.U. These pairs present a diversity of functional group substitutions in the context of a wobble conformation. Comparison of wobble pairs with and without the N2 exocyclic amine, i.e., G.U vs I.U, DAP.MeiC vs A.MeiC, and DAP.C vs A.C, demonstrates that the amine does not contribute to base pairing stability when the pair is located at the terminal position of the RNA duplex. However, at a position internal to the duplex, the exocyclic amine does improve helix stability. An internal I.U pair is less stable (approximately 1 kcal.mol-1) than an internal G.U pair, and substantially less stable (approximately 2 kcal.mol-1) than an internal A-U pair. These data provide quantitation for the reduced duplex stability observed upon conversion of A-U to I.U pairs by double-stranded RNA adenosine deaminase (dsRAD). This collection of wobble pairs will help identify the contribution made by individual functional groups in RNA/protein interactions and in the tertiary folding of RNA.

2-Aminopurine↗
PubMedDate not supplied

Synthesis of 2'-O-substituted ribonucleosides.

An efficient synthesis of 2'-O-substituted ribonucleosides, including 2'-O-TBDMS and 2'-O-TOM protected as well as 2'-O-Me and 2'-O-allyl derivatives is presented. Di-t-butylsilylene group was employed for simultaneous protection of 3'- and 5'- hydroxyl functions of nucleoside on the first step. Subsequent silylation or alkylation of free 2'-OH followed by introduction of suitable protection on the base moiety and removal of cyclic silyl protection gave target compounds in a high yield.

Alkylation↗
PubMedDate not supplied

Synthesis of 1,4-anhydro-2-deoxy-D-ribitol derivatives from thymidine.

1,2-Dideoxyribose 5-O-succinate, a component of solid support employed in the synthesis of ribozymes, was synthesized from thymidine. The key step was elimination of nucleobase from 2 to afford glycal 3. A number of catalysts for this reaction were tested, resulting in improved and scaleable synthesis. Hydrogenation of the resulting glycal afforded 1,2-dideoxyribose derivative 4 in a high yield.

Deoxyribose↗