Indiana University

Advanced Research & Technology Institute

Amira, Inc.

Theodore S Widlanski

Jeffrey Brian Epp

Rima Kaddurah-Daouk

Jonathan J Burbaum

C Cheng Kao

Craig J Forsyth

James W Lillie

William Vassiliou

The invention provides methods and compositions for polymerizing a particular nucleotide with a polymerase. In general, the method involves (a) forming a mixture of a polymerase and a nucleoside triphosphate (NTP) comprising &agr;, &bgr; and &ggr; phosphates and a &ggr;-phosphate phosphoester-linked functional group; and incubating the mixture under conditions wherein the polymerase catalyzes cleavage of the NTP between the &agr; and &bgr; phosphates, liberating a pyrophosphate comprising the functional group and polymerizing the resultant nucleoside monophosphate, i.e. incorporates the nucleoside monophosphate in a nascent polynucleotide. A variety of functional groups compatible with the polymerization reaction are provided.

&ggr;-phosphoester nucleoside triphosphates

Analogues of RNA and DNA compounds contain a neutral, stereoregular linking group based on replacement of the phosphoryl with a sulfonyl group. Precursors to the analogues are also described, as are methods for preparing the precursors and analogues.

Nucleotides and oligonucleotides preparable therefrom

Described are preferred suicide inhibitors of phosphatase or phosphodiesterase enzymes, and methods for preparing halo enol phosphates which can serve as such suicide inhibitors.

Phosphatase/phosphodiesterase enzyme inhibitors and methods

3'-sulfonyl nucleoside compounds

The present invention relates to the use of analogs of creatine, such as cyclocreatine, as antiviral agents. Analogs of creatine can be used as antiviral agents against a variety of viruses, particularly DNA viruses, such as Herpes viruses (e.g., HSV-1, HSV-2, cytomegaloviruses, Varicella-Zoster virus) and adenovirus. The invention further relates to creatine analogs including four classes of creatine analogs selected as candidate antiviral compounds: (1) creatine analogs that can be phosphorylated by creatine kinase but differ in their phosphoryl group transfer potential, (2) bisubstrate inhibitors of creatine kinase comprising covalently linked structural analogs of adenosine triphosphate (ATP) and creatine, (3) creatine analogs which can act as irreversible inhibitors of creatine kinase, and (4) N-phosphorocreatine analogs bearing non-transferable moieties which mimic the N-phosphoryl group.

Creatine analogs having antiviral activity

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Bloomington, IN, United States of America

Theodore S Widlanski