Semisynthesis of 6-chloropurine-2'-deoxyriboside 5'-dimethoxytrityl 3'-(2-cyanoethyl-N,N-diisopropylamino)phosphoramidite and its use in the synthesis of fluorescently labeled oligonucleotides.
An efficient enzymatic synthesis of 6-chloropurine-2'-deoxyriboside from the reaction of 6-chloropurine with 2'-deoxycytidine catalyzed by nucleoside-2'-deoxyribosyltransferase (E.C. 2.4.2.6) followed by chemical conversion into the 5'-dimethoxytrityl 3'-(2-cyanoethyl-N,N-diisopropylamino) phosphoramidite derivative is described. The phosphoramidite derivative was incorporated site-specifically into an oligonucleotide and used for the introduction of a tethered tetramethylrhodamine-cadaverine conjugate. The availability of an efficient route to 6-chloropurine-2'-deoxyriboside 5'-dimethoxytrityl 3'-(2-cyanoethyl-N,N-diisopropylamino)phosphoramidite enables the facile synthesis of oligonucleotides containing a range of functional groups tethered to deoxyadenosine residues.
A. B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Md Jashim
MJ
Uddin
Michael I
MI
Schulte
Leena
L
Maddukuri
Joel
J
Harp
Lawrence J
LJ
Marnett
D002103:Cadaverine / Q000737:chemistry; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003461:Crystallography; D005456:Fluorescent Dyes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010430:Pentosyltransferases / Q000378:metabolism*; D011684:Purine Nucleosides / Q000096:biosynthesis* / Q000138:chemical synthesis* / Q000737:chemistry; D011687:Purines / Q000737:chemistry; D012235:Rhodamines / Q000737:chemistry; D013050:Spectrometry, Fluorescence
D005456:Fluorescent Dyes; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D011684:Purine Nucleosides; D011687:Purines; D012235:Rhodamines; C005358:tetramethylrhodamine; D010430:Pentosyltransferases; C021888:nucleoside deoxyribosyltransferase; D002103:Cadaverine; C079308:6-chloropurine