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Oligonucleotide Analogues (oligonucleotide + analogue)

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Chemistry	100%

Selected Abstracts

Oligonucleotide Analogues with Integrated Bases and Backbone.

HELVETICA CHIMICA ACTA, Issue 5 2007
Part 1
Abstract The self-complementary (Z)-configured U*[ce]A(*) dinucleotide analogues 6, 8, 10, 12, 14, and 16, and the A*[ce]U(*) dimers 19, 21, 23, 25, 27, and 29 were prepared by partial hydrogenation of the corresponding ethynylene linked dimers. Photolysis of 14 led to the (E)-alkene 17. These dinucleotide analogues associate in CDCl3 solution, as evidenced by NMR and CD spectroscopy. The thermodynamic parameters of the duplexation were determined by van't Hoff analysis. The (Z)-configured U*[ce]A(*) dimers 14 and 16 form cyclic duplexes connected by Watson,Crick H-bonds, the (E)-configured U*[ce]A dimer 17 forms linear duplexes, and the U*[ce]A(*) allyl alcohols 6, 8, 10, and 12 form mixtures of linear and cyclic duplexes. The C(6/I)-unsubstituted A*[ce]U allyl alcohols 19 and 23 form linear duplexes, whereas the C(6/I)-substituted A*[ce]U* allyl alcohols 21 and 25, and the C(5,/I)-deoxy A*[ce]U(*) dimers 27 and 29 also form minor amounts of cyclic duplexes. The influence of intra- and intermolecular H-bonding of the allyl alcohols and the influence of the base sequence upon the formation of cyclic duplexes are discussed. [source]

Oligonucleotide Analogues with Integrated Bases and Backbone.

HELVETICA CHIMICA ACTA, Issue 4 2007
Part 1
Abstract The self-complementary tetrameric propargyl triols 8, 14, 18, and 21 were synthesized to investigate the duplex formation of self-complementary, ethynylene-linked UUAA, AAUU, UAUA, and AUAU analogues with integrated bases and backbone (ONIBs). The linear synthesis is based on repetitive Sonogashira couplings and C -desilylations (34,72% yield), starting from the monomeric propargyl alcohols 9 and 15 and the iodinated nucleosides 3, 7, 11, and 13. Strongly persistent intramolecular H-bonds from the propargylic OH groups to N(3) of the adenosine units prevent the gg -type orientation of the ethynyl groups at C(5,). As such, an orientation is required for the formation of cyclic duplexes, this H-bond prevents the formation of duplexes connected by all four base pairs. However, the central units of the UAUA and AAUU analogues 18 and 14 associate in CDCl3/(D6)DMSO 10,:,1 to form a cyclic duplex characterized by reverse Hoogsteen base pairing. The UUAA tetramer 8 forms a cyclic UU homoduplex, while the AUAU tetramer 21 forms only linear associates. Duplex formation of the O -silylated UUAA and AAUU tetramers is no longer prevented. The self-complementary UUAA tetramer 22 forms Watson,Crick - and Hoogsteen -type base-paired cyclic duplexes more readily than the sequence-isomeric AAUU tetramer 23, further illustrating the sequence selectivity of duplex formation. [source]

Oligonucleotide Analogues with Integrated Bases and Backbone.

HELVETICA CHIMICA ACTA, Issue 12 2006

Abstract The self-complementary UA and AU dinucleotide analogues 41,45, 47, 48, and 51,60 were prepared by Sonogashira coupling of 6-iodouridines with C(5,) -ethynylated adenosines and of 8-iodoadenosines with C(5,) -ethynylated uridines. The dinucleotide analogues associate in CDCl3 solution. The C(6/I) -unsubstituted AU dimers 51 and 54 prefer an anti -oriented uracilyl group and form stretched linear duplexes. The UA propargyl alcohols 41 and 43,45 possess a persistent intramolecular O(5,/I)H,,,N(3/I) H-bond and, thus, a syn -oriented adeninyl and a gt - or tg -oriented ethynyl moiety; they form corrugated linear duplexes. All other dimers form cyclic duplexes characterized by syn -oriented nucleobases. The preferred orientation of the ethynyl moiety (the C(4,),C(5,) torsion angle) defines a conformation between gg and one where the ethynyl group eclipses O(4,/I). The UA dimers 42, 47, and 48 form Watson,Crick H-bonds, the AU dimers 56 and 58,60 H-bonds of the Watson,Crick -type, the AU dimers 53 and 55 reverse- Hoogsteen, and 57Hoogsteen H-bonds. The pairing mode depends on the substituent of C(5,/I) (H, OSiiPr3; OH) and on the H-bonds of HOC(5,/I) in the AU dimers. Association constants were derived from the concentration-dependent chemical shift for HN(3) of the uracilyl moiety; they vary from 45,104,M,1 for linear duplexes to 197,2307,M,1 for cyclic duplexes. The thermodynamic parameters were determined by van't Hoff analysis of the temperature-dependence of the (concentration-dependent) chemical shift for HN(3) of the uracilyl moiety. Neglecting stacking energies, one finds an average energy of 3.5,4.0,kcal/mol per intermolecular H-bond. Base stacking is evidenced by the temperature-dependent CD spectra. The crystal structure of 54 shows two antiparallel chains of dimers connected by Watson-Crick H-bonds. The chains are bridged by a strong H-bond between the propargylic OH and OC(4) and by weak reverse A,,,A Hoogsteen H-bonds. [source]

Conformational evaluation of labeled C3,-O-P- 13CH2 -O-C4, phosphonate internucleotide linkage, a phosphodiester isostere

BIOPOLYMERS, Issue 7 2009

Abstract Modified internucleotide linkage featuring the C3,-O-P-CH2 -O-C4, phosphonate grouping as an isosteric alternative to the phosphodiester C3,-O-P-O-CH2 -C4, bond was studied in order to learn more on its stereochemical arrangement, which we showed earlier to be of prime importance for the properties of the respective oligonucleotide analogues. Two approaches were pursued: First, the attempt to prepare the model dinucleoside phosphonate with 13C-labeled CH2 group present in the modified internucleotide linkage that would allow for a more detailed evaluation of the linkage conformation by NMR spectroscopy. Second, the use of ab initio calculations along with molecular dynamics (MD) simulations in order to observe the most populated conformations and specify main structural elements governing the conformational preferences. To deal with the former aim, a novel synthesis of key labeled reagent (CH3O)2P(O)13CH2OH for dimer preparation had to be elaborated using aqueous 13C-formaldehyde. The results from both approaches were compared and found consistent. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 514,529, 2009. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source]