Synthesis and characterization of imidazoyl-linked synthons and 3'-conjugated thymidine derivatives

Alternative Procedures for the Synthesis of Methionine-Containing Peptide−Oligonucleotide Hybrids

“…Literature reports on the compatibility of the conditions required to deprotect His(Trt) and the stability of the glycosidic linkage are somewhat contradictory. [3,28] Amino acid coupling problems were similarly encountered when we undertook the synthesis of Phac-His-GlyMet-linker-dCATGGCT (5). Only the use of the strongest carboxyl activating agents, such as HATU, [29] was found to allow quantitative coupling of the methionine and glycine derivatives, but incorporation of the histidine residue never exceeded 20% yield.…”

“…The target product (5) was finally obtained by HATU-mediated coupling of the tripeptide PhacHis(Dnp)-Gly-Met-OH to the linker-oligonucleotideresin. [28] For amino acid or peptide couplings to H 2 N-linker-oligonucleotide-resins, some authors have reported low or nonreproducible yields. [9] Other authors have not described any particular problems in relation to the stepwise elongation of a peptide on an oligonucleotideϪresin using Fmoc-amino acids, [3] whereas others have encountered more difficulties in the coupling of the first Fmoc-amino acid than in the subsequent couplings.…”

History of Research on Antisense Oligonucleotide Analogs

“…100 Knorre et al provide an extensive list of such reactive groups. 101 We attached imidazole to the terminus of an oligonucleotide 102 in order to try to reproduce the catalytic effect of RNase, since the catalytic effect depends on imidazoles in the active site. 103 Since then much progress has been made in synthesizing oligos containing one, 104-106 two 107 or multiple imidazole groups 108 to mimic the catalytic activity of ribonuclease using tRNA as a target.…”

Syntheses and Oligonucleotide Incorporation of Nucleoside Analogues Containing Pendant Imidazolyl or Amino Functionalities – The Search for Sequence‐Specific Artificial Ribonucleases

“…[12] Beban and Miller used post-synthetic modification to conjugate imidazole units to a 2Ј-modified 2Ј-deoxyuridine nucleoside, [13] whilst Polushin conjugated histidine or imidazoleacetic acid to the 3Ј-position of thymidine for incorporation at the 3Ј-terminus of oligonucleotides. [14] Unfortunately, no RNA cleavage assays were reported using these derivatives.…”