Lynx Therapeutics, Inc.

Applied Biosystems, LLC

Polaroid Corporation

Bernard L Hirschbein

Karen L Fearon

Sergei M Gryaznov

Ronald G Schultz

Bogdan Uznanski

Wojciech J Stec

B John Bergot

Sarah N McCurdy

Stephen J Telfer

Edward P Lindholm

Michael J Zuraw

Karen L Fearson

Jeffery S Nelson

Jeffrey S Nelson

The invention provides a method of synthesizing oligonucleotide N3'.fwdarw.P5' phosphoramidates using an amine-exchange reaction of phosphoramidites in which a -deprotected 3'-amino group of a solid phase supported oligonucleotide chain is exhanged for the amino portion of a 5'-phosphoramidite of an incoming monomer which has a protected 3'-amino group. The resulting internucleotide phosphoramidite linkage is then oxidized to form a stable protected phosphoramidate linkage. The method of the invention greatly improves product yields and reduces reagent usage over currently available methods for synthesizing the above class of compound.

Synthons for synthesis of oligonucleotide N3-P5 phosphoramidates

The invention provides a method of synthesizing oligonucleotide N3'.fwdarw.P5' phosphoramidates using an amine-exchange reaction of phosphoramidites in which a deprotected 3'-amino group of a solid phase supported oligonucleotide chain is exhanged for the amino portion of a 5'-phosphoramidite of an incoming monomer which has a protected 3'-amino group. The resulting internucleotide phosphoramidite linkage is then oxidized to form a stable protected phosphoramidate linkage. The method of the invention greatly improves product yields and reduces reagent usage over currently available methods for synthesizing the above class of compound.

Solid phase synthesis of oligonucleotide N3'-P5' phosphoramidates

An imaging medium capable of being imaged to form a transparency comprises a substantially transparent support having a thickness of at least about 20 .mu.m, a color-forming layer superposed on the support and comprising a color-forming composition adapted to undergo a change of color upon increase in the temperature of the color-forming layer above a color-forming temperature for a color-forming time; and a bubble-suppressant layer superposed on the color-forming layer and having a thickness of at least about 10 .mu.m. Upon imagewise increase in the temperature of the color-forming layer above the color-forming temperature for the color-forming time, in heated regions the color-forming layer undergoes its change of color but remains essentially free from bubbles, thereby providing an image in which the colored regions are not blackened when viewed in transmission.

Imaging medium with bubble-suppressant layer

A method for synthesizing sulfurized oligonucleotide analogs, such as phosphorothioate and phosphorodithioate analogs, is provided that employs a thiophosphorus compound, such as a thiophosphoric, dithiophosphoric, thiophosphinic, or dithiophosphinic acid disulfide or polysulfide, as a sulfurizing agent. The method of the invention may be used to sulfurize any phosphorous(III)containing intermediate. Preferably, the method is practiced on a commercial DNA synthesizer using phosophoramidite and/or phosphorthioamidite intermediates.

Method of synthesizing sulfurized oligonucleotide analogs

A method for synthesizing sulfurized oligonucleotide analogs, such as phosphorothioate and phosphorodithioate analogs, is provided that employs a thiuram disulfide as a sulfurizing agent. The method of the invention may be used to sulfurize any phosphorous(III)-containing intermediate. Preferably, the method is practiced on a commercial DNA synthesizer using phosphoramidite and/or phosphorthioamidite intermediates.

Method of synthesizing sulfurized oligonucleotide analogs with thiuram

A method for synthesizing sulfurized oligonucleotide analogs, such as phosphorothioate and phosphorodithioate analogs, is provided that employs a thiophosphorus compound, such as a thiophosphoric, dithiophosphoric, thiophosphinic, or dithiophosphinic acid disulfide or polysulfide, as a sulfurizing agent. The method of the invention may be used to sulfurize any phosphorous(III)-containing intermediate. Preferably, the method is practiced on a commercial DNA synthesizer using phosphoramidite and/or phosphorthioamidite intermediates.

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San Francisco, CA, United States of America

Bernard L Hirschbein