Synthesis, Biophysical and Biological Evaluations of Novel Antisense Oligonucleosides Containing Dephosphono-Internucleosidic Linkages

Yogesh S. Sanghvi Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Laurent Bellon Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Francęois Morvan Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Tomonori Hoshiko Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Eric Swayze Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Lendell Cummins Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Susan Freier Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Nicholas Dean Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Brett Monia Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

Richard H. Griffey Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

P. Dan Cook Medicinal Chemistry Department, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, CA, 92008, U.S.A.

show all

Abstract

Efficient large-scale syntheses of methylene(methylimino) (MMI) linked mixed base nucleosidic dimers have been accomplished. These dimers were successfully incorporated into deoxyoligonucleotides by automated solid-support synthesis. The hybridization properties, nuclease stability, RNase H mediated cleavage and in vitro biological activity of novel chimeric oligomers have been studied. The biophysical and biological evaluation of these chimeric oligomers containing MMI linkages suggests that MMI is a promising chemical modification of the backbone linkage for the construction of antisense molecules useful as therapeutics.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Synthesis, Biophysical and Biological Evaluations of Novel Antisense Oligonucleosides Containing Dephosphono-Internucleosidic Linkages

Information for

Open access

Opportunities

Help and information

Synthesis, Biophysical and Biological Evaluations of Novel Antisense Oligonucleosides Containing Dephosphono-Internucleosidic Linkages

Abstract

Reprints and Corporate Permissions

Academic Permissions

Related research

To cite this article:

Download citation

Information for

Open access

Opportunities

Help and information

Keep up to date

Your download is now in progress and you may close this window

Login or register to access this feature