Enzymatically stable 5' mRNA cap analogs: synthesis and binding studies with human DcpS decapping enzyme.
Four novel 5' mRNA cap analogs have been synthesized with one of the pyrophosphate bridge oxygen atoms of the triphosphate linkage replaced with a methylene group. The analogs were prepared via reaction of nucleoside phosphor/phosphon-1-imidazolidates with nucleoside phosphate/phosphonate in the presence of ZnCl2. Three of the new cap analogs are completely resistant to degradation by human DcpS, the enzyme responsible for hydrolysis of free cap resulting from 3' to 5' cellular mRNA decay. One of the new analogs has very high affinity for binding to human DcpS. Two of these analogs are Anti Reverse Cap Analogs which ensures that they are incorporated into mRNA chains exclusively in the correct orientation. These new cap analogs should be useful in a variety of biochemical studies, in the analysis of the cellular function of decapping enzymes, and as a basis for further development of modified cap analogs as potential anti-cancer and anti-parasite drugs.
Kalek
Marcin
M
Department of Biophysics, Experimental Physics Institute, Warsaw University, Zwirki i Wigury 93, 02-089 Warsaw, Poland.
Jemielity
Jacek
J
Darzynkiewicz
Zbigniew M
ZM
Bojarska
Elzbieta
E
Stepinski
Janusz
J
Stolarski
Ryszard
R
Davis
Richard E
RE
Darzynkiewicz
Edward
E
D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D015394:Molecular Structure; D012315:RNA Caps / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D017186:Titrimetry
D012315:RNA Caps; D004722:Endoribonucleases; C485332:DcpS protein, human