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Syntheses and Oligonucleotide Incorporation of Nucleoside Analogues Containing Pendant Imidazolyl or Amino Functionalities – The Search for Sequence‐Specific Artificial Ribonucleases
Author(s) -
Holmes Stephen C.,
Gait Michael J.
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500413
Subject(s) - oligonucleotide , chemistry , phosphoramidite , rnase p , nuclease , ribonuclease , nucleoside , combinatorial chemistry , nucleotide , nucleic acid , sequence (biology) , rnase h , oligonucleotide synthesis , stereochemistry , biochemistry , rna , enzyme , dna , gene
Oligonucleotide derivatives containing imidazolyl and amino functionalities have been proposed as artificial ribonucleases that might mimic the activities of RNase A but with greater sequence specificity. Such oligonucleotide reagents would have important applications as enhanced antisense reagents that obviate the need to recruit a cellular nuclease or nuclease complex. We present the syntheses of six nucleoside phosphoramidite analogues containing pendant protected imidazolyl or amino groups and their incorporation into oligonucleotides. We show that the six functionalised phosphoramidites have similar efficiencies of incorporation and present mass spectral evidence that the composition of an oligonucleotide library of 81 components is consistent with the expected mass mixture distribution. Such phosphoramidites are thus suitable starting materials for construction of mixed oligonucleotide libraries containing a region of imidazolyl and amino‐modified nucleotides ready for screening for sequence‐specific ribonuclease activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)