3′‐Deoxy‐3′‐aminonucleoside 5′‐triphosphates — Terminators of RNA synthesis, catalyzed by DNA‐dependent RNA polymerase from Escherichia coli

Abstract

not receivedEscherichia coli

3′‐Hydroxymethyl 2′‐deoxynucleoside 5′‐triphosphates are inhibitors highly specific for reverse transcriptase

“…A wide variety of nucleoside 5'-triphosphates modified at the sugar moiety was tested as chain terminators for a number of polynucleotide synthesizing enzymes [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Among these we have found dNTP(3'-NH2) which is equally active against most of the tested DNA polymerases [7][8][9][10][11][12], araNTP(3'-NH2) which is active against all but E. coli DNA polymerase I [9,10], dNTP(3'-Nfluoroscaminyl) which is not inhibitory only for the terminal deoxyribonucleotidyl transferase [10], and dNTP(3'-N3) and araNTP(3'-N3) active against AMV reverse transcriptase [10,12].…”

Molecular bases for the action and selectivity of nucleoside antibiotics

“…This mode of action resembles that of 3'-deoxyadenosine (Cordycepin) very closely.222 This finding has recently been confirmed by a number of synthetic 3'-NH,-nucleotides where RNA synthesis has been studied using purified E. culi DNA-dependent RNA polymerase. 223 3'-NH3-3dA is also a substrate of ATPKTP: tRNA nucleotidyl transferase, and thus, a tRNA molecule can be obtained with a 3'-NH2-deoxyadenosine in the 3' end. Although it can bind an aminoacyl moiety to the 3'-amino groups, it is not a substrate to the peptidyl-transferase because it is unable to cleave the amide group.z"226 3'-NH2-3'dA has also antiherpes activity at concentrations that are not harmful to human cells (see Figure 29).…”

2‘,3‘-Dideoxy-3‘-thionucleoside Triphosphates: Syntheses and Polymerase Substrate Activities

“…The 3‘-amino-2‘,3‘-dideoxynucleoside triphosphates or 3‘-amino-3‘-deoxynucleoside triphosphates place an amino group on the dNTP or NTP 3‘-carbon. These derivatives are reported to function as inhibitors of DNA or RNA polymerases, with the former acting largely as chain terminators after the initial nucleotide elongation event.…”