title: Enzymatically stable 5' mRNA cap analogs: synthesis and binding studies with human DcpS decapping enzyme.
abstract: 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.
authors.affiliation: Department of Biophysics, Experimental Physics Institute, Warsaw University, Zwirki i Wigury 93, 02-089 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kalek
authors.forename: Jacek
authors.initials: J
authors.lastname: Jemielity
authors.forename: Zbigniew M
authors.initials: ZM
authors.lastname: Darzynkiewicz
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Bojarska
authors.forename: Janusz
authors.initials: J
authors.lastname: Stepinski
authors.forename: Ryszard
authors.initials: R
authors.lastname: Stolarski
authors.forename: Richard E
authors.initials: RE
authors.lastname: Davis
authors.forename: Edward
authors.initials: E
authors.lastname: Darzynkiewicz
mesh_terms: 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
chemical_list: D012315:RNA Caps; D004722:Endoribonucleases; C485332:DcpS protein, human