Radiosynthesis of new [90Y]-DOTA-based maleimide reagents suitable for the prelabeling of thiol-bearing L-oligonucleotides and peptides.
We describe the radiosynthesis of two new [(90)Y]-DOTA-based maleimide reagents, suitable for the mild radiolabeling of L-RNAs and peptides modified with thiol-bearing linkers. The synthesis procedure of both maleimide-bearing (90)Y complexes, [{(2S)-2-[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl}tetraacetato][(90)Y]yttrate(1-)([(90)Y]3) and [{(2S)-2-(4-{[4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoyl]amino}benzyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetrayl]tetraacetato}[(90)Y]yttrate(1-)([(90)Y]4), was optimized in terms of an easy purification method via solid-phase extraction (SPE). Application as well as reactivity of both maleimide reagents were initially evaluated by the prelabeling of glutathione (GSH) and a thiol-modified 12mer L-RNA as model substances. In comparison to the N-aryl maleimide-bearing complex [(90)Y]3, N-alkyl maleimide-bearing complex [(90)Y]4 showed an increased hydrolytic stability at pH > or = 7. A slightly higher reactivity was found for [(90)Y]3 by prelabeling of 0.1 and 1 microg glutathione, respectively, in phosphate buffer (pH 7.2) at room temperature. In terms of very high radiochemical yields, the direct radiolabeling of DOTA-L-RNA conjugate with [(90)Y]YCl(3) proved to be more suitable than the prelabeling of the thiol-modified 12mer L-RNA derivative with [(90)Y]4.
Schlesinger
Joern
J
Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, Germany.
Fischer
Cindy
C
Koezle
Inge
I
Vonhoff
Stefan
S
Klussmann
Sven
S
Bergmann
Ralf
R
Pietzsch
Hans-Jurgen
HJ
Steinbach
Joerg
J
D005978:Glutathione / Q000032:analysis / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D009841:Oligonucleotides / Q000032:analysis / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000032:analysis / Q000737:chemistry*; D012313:RNA / Q000032:analysis / Q000737:chemistry; D052616:Solid Phase Extraction; D013438:Sulfhydryl Compounds / Q000737:chemistry; D015021:Yttrium Radioisotopes / Q000737:chemistry
D006571:Heterocyclic Compounds; D008301:Maleimides; D009841:Oligonucleotides; D009942:Organometallic Compounds; D010455:Peptides; D013438:Sulfhydryl Compounds; D015021:Yttrium Radioisotopes; C113625:yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; C043592:maleimide; D012313:RNA; D005978:Glutathione