Reported here are the results of a search for modified oligodeoxynucleotides with a 5'-terminal cytidine residue whose affinity for target strands is enhanced by 5'-acylamido groups. These acylamido groups were envisioned to act as molecular caps that bind to the exposed terminal base pair of the duplex with the target strand. A total of 52 capped oligonucleotides of the sequence R-CGGTTGAC, where R denotes the 5'-appendage and C a 5'-amino-2',5'-dideoxycytidine residue, were tested. Among the building blocks employed to modify the 5'-amino group of the DNA strand were carboxylic acid residues, either appended directly or via an amino acid residue, and aromatic aldehydes, coupled via reductive amination. The carboxylic acids employed ranged from Fmoc-glycine to (Fmoc)(2)-vancomycin and included a number of aromatic acids and bile acids. Small libraries were subjected to MALDI-monitored nuclease selection experiments, and selected compounds were tested in UV-melting assays with target strands. Cholic acid appendages stabilized terminal C:G base pairs to the greatest extent, with melting point increases of up to 10 degrees C. Further, the cholic acid residue enhanced base pairing fidelity at the terminus, as determined in melting analyses with target strands containing a mismatched nucleobase at the 3'-terminus.
Stereoisomerization of Ketene lminesBarriers to racemization in solution of the ketene imines 1 a -y and X-ray structures of the ketene imines 1 s and z are described. Similar to allenes all ketene imines have dihedral angles of 90" between the C-and N-substituents. The barriers to racemization range from 30 to 63 kJmol-' and are lowered by electron attracting substituents on C and N. The barriers of m-and p-substituted N-arylketene imines give a linear Hamme// correlation with 0 -constants. N-Arylketene imines racemize through inversion at nitrogen and simultaneous rotation of the aryl group around the N -aryl bond.Ketenimine 1 sollten wie Allene gebaut sein, bei denen ein Substituent durch ein freies Elektronenpaar ersetzt ist. Am C-Ende ungleich substituierte Ketenimine (1, R' # R2) waren also chiral.Die Frage nach dem raumlichen Bau von Keteniminen ist nicht trivial, denn die isoelektronischen Cyanamidiumsalze 2 haben beispielsweise ein lineares Molekiilgerust N -C = N -C mit C2,.-Symmetrie, sind also auch fur R' # R2 achiral'). Nach einer Rontgenstrukturanalyse2) ist weiterhin das C = C = N -C-Gerust des Ketenimins 3 linear gebaut und weist eine kurze Kumulen-CN-Bindung von nur 115 pm auf, wie sie typisch fur Nitriliumsalze ist 3). Ahnlich sind einige andere Ketenimine g e b a~t~.~) .Erst neuerdings wurden Kristallstrukturen von Keteniminen mit allenartigem Molekulgeriist 1 mit CiSymmetrie und einer Lange der C = N-Doppelbindung von 122 pm bekannt6).Nach diesen Befunden mu8 man vermuten, daR der Energieunterschied zwischen der gewinkelten Form 1 und der linearen Anordnung 3 nicht gro8 ist, da8 Ketenimine mit R' # R2 also ahnlich wie Carbodiimide') in Losung bereits bei tiefen Temperaturen Chem. Ber. 114(1981) +
Wegen ihrer ganz anderen chemischen und physikalischen Eigenschaften sollte man unserer Meinung nach Verbindungen der Art 1 und 2, bei denen die kumulierten Doppelbindungen nicht
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