Abstract: Modified oligonucleotides 3′-NHP(O)(O−)O-5′ phosphoramidates were synthesized on a solid phase support. The phosphoramidate analogs were found to have significantly increased resistance toward phosphodiesterase digestion. Thermal dissociation experiments demonstrated that these compounds form more stable duplexes than phosphodiesters with complementary DNA and particularly RNA strands. Further, the phosphoramidate analogs can also form stable triplexes with double-stranded DNA target, where under similar conditions parent phosphodiester compounds failed to do so.
Type:
Grant
Filed:
September 3, 1997
Date of Patent:
January 2, 2001
Assignee:
Lynx Therapeutics, Inc.
Inventors:
Sergei M. Gryaznov, Ronald G. Schultz, Jer-kang Chen
Abstract: Modified oligonucleotides 3'-NHP(O)(O.sup.-)O-5' phosphoramidates were synthesized on a solid phase support. The phosphoramidate analogs were found to have significantly increased resistance toward phosphodiesterase digestion. Thermal dissociation experiments demonstrated that these compounds form more stable duplexes than phosphodiesters with complementary DNA and particularly RNA strands. Further, the phosphoramidate analogs can also form stable triplexes with double-stranded DNA target, where under similar conditions parent phosphodiester compounds failed to do so.
Type:
Grant
Filed:
January 10, 1997
Date of Patent:
October 12, 1999
Assignee:
Lynx Therapeutics, Inc.
Inventors:
Sergei M. Gryaznov, Ronald G. Schultz, Jer-kang Chen
Abstract: Modified oligonucleotides 3'-NHP(O)(O.sup.-)O-5' phosphoramidates were synthesized on a solid phase support. The phosphoramidate analogs were found to have significantly increased resistance toward phosphodiesterase digestion. Thermal dissociation experiments demonstrated that these compounds form more stable duplexes than phosphodiesters with complementary DNA and particularly RNA strands. Further, the phosphoramidate analogs can also form stable triplexes with double-stranded DNA target, where under similar conditions parent phosphodiester compounds failed to do so.
Type:
Grant
Filed:
June 6, 1995
Date of Patent:
November 17, 1998
Assignee:
Lynx Therapeutics, Inc.
Inventors:
Sergei M. Gryaznov, Ronald G. Schultz, Jer-kang Chen
Abstract: A novel human serine protein kinase, human p21-protein activated serine kinase p65 protein, referred to as hPAK65, and methods for its preparation and use are provided. Nucleic acids encoding hPAK65 and methods for their use in preparing hPAK65 as well as in preparing and identifying hPAK65 analogs are provided. Methods provided for the use of hPAK65 protein and its protein fragments, such as those that retain at least one hPAK65 activity, that include screening libraries of agents for candidates that modulate hPAK65 activity. Methods are provided to identify agents that modulate the interaction of hPAK65 with rho-like p21 GTPases, particularly rac1 and CDC42Hs binding to hPAK65 and subsequent activation of hPAK65 serine protein kinase activity, that modulate hPAK65 serine protein kinase activity, and that modulate hPAK65 effect on p21 protein GTPase activity.