Oligonucleotides with novel, cationic backbone substituents: aminoethylphosphonates.

Content Provider	Semantic Scholar
Author	Fathi, R. Huang, Qingqiu Coppola, Gabriele Delaney, William Teasdale, Rebecca Krieg, Arthur M. Cook, Alan F.
Copyright Year	1994
Abstract	Oligonucleotide (2-aminoethyl)phosphonates in which the backbone consisted of isomerically pure, alternating (2-aminoethyl)-phosphonate and phosphodiester linkages have been prepared and characterized. One of these single isomer oligonucleotides (Rp) formed a more stable duplex with DNA or RNA than its corresponding natural counterpart. Hybrid stability was more pH-dependent, but less salt-dependent than a natural duplex. The specificity of hybridization was examined by hybridization of an oligonucleotide containing one (2-aminoethyl)phosphonate to oligonucleotides possessing mismatches in the region opposite to the aminoethyl group. In contrast to oligonucleotides containing (aminomethyl)-phosphonate linkages, oligonucleotide (2-aminoethyl)phosphonates were completely stable to hydrolysis in aqueous solution. These oligonucleotides were resistant to nuclease activity but did not induce RNase H mediated cleavage of a complementary RNA strand. Incubation in a serum-containing medium resulted in minimal degradation over 24 hours. Studies of cell uptake by flow cytometry and confocal microscopy demonstrated temperature dependent uptake and intracellular localization. (2-Aminoethyl)phosphonates represent a novel approach to the introduction of positive charges into the backbone of oligonucleotides.
Starting Page	234501
Ending Page	234501
Page Count	1
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/nar/22/24/10.1093/nar/22.24.5416/2/22-24-5416.pdf?Expires=1492496963&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=D6~ygRdm50WVCqCOEWBna7hyYc-i-9QHbgq2zcWufBwPHiIo1GEdiA6xZoi~q-cKnEZZtcqeRNgm~Yza5yyqA-D5xREZjheezun6w5PxOZ1QW2CCY-NFqQu8TEEUGuMFmYp27i9G1dLyVgftl4Vduc-yd39miPPJCdUIT4fkjuFEYD9ErraYQ0CBfC~clpU2Qk2QjDW9484C3x9rnc3zkkOAw34Hi7cQWOrCSlMiFRbewBVtM1ZRT1uxbyWpxiZS9-pSQOcYYZUjkDKuzGMP7ffjRbGP4yBINo68yNIqyYnxz6FrivOjE6JZVyxAhCrxo8CmFn0Ug1mvwaRg4UXVrg__
PubMed reference number	7816633v1
Volume Number	22
Issue Number	24
Journal	Nucleic acids research
Language	English
Access Restriction	Open
Subject Keyword	Cell Nucleus Complementary RNA Ephrin Type-B Receptor 1, human Flow Cytometry Hybrids International System of Units Isomerism Microscopy, Confocal N-methyl-aminomethyl-P-hydroxymethylphosphinic acid New type Nucleic Acid Hybridization Nucleic Acids Nucleotides Oligonucleotides Phosphonates Phosphorus Stereoisomers Thy-1 Antigens Vertebral column antisense therapy beta-Aminoethyl Isothiourea carbene nuclease activity organic phosphonate catabolic process phosphodiester ribonuclease T2 activity
Content Type	Text
Resource Type	Article