The United States of America As Represented by the Department of Health

The United States of America, As Represented by the Secretary, Department of Health and Human Services

The Government of the United States of America, As Represented by the

James A Kelley

Victor E Marquez

John S Driscoll

Hiroaki Mitsuya

Christopher K-h Tseng

David G Johns

Terrence R Burke, Jr

Joseph J Barchi, Jr

Kyung S Lee

Jung Eun Park

Harry Ford, Jr

Christopher C Lai

Joseph E Tomaszewski

Wenjian Qian

Chong-Ho Kim

The invention provides novel compounds that may serve as anticancer therapeutics. The compounds of the invention bind to polo-like kinases through the polo-box domain. In certain embodiments, the compounds of the invention are POM-protected peptide derivatives. The use of cationic bis-alkyl his residues in combination with a mono POM-protected phophoryl group results in a peptide possessing an overall neutral charge. The peptide derivatives of the invention have achieved both good efficacy and an enhanced bioavailability. The invention also provides methods of use, compositions, and kits thereof. Further, the invention provides a novel method of design and/or synthesis of phosphoryl-derived peptide derivatives useful as therapeutic agents.

Peptide and peptide mimetic binding antagonists of polo-like kinase 1 polo box domain and methods of use

Methods of treating a human infected with human immunodeficiency virus (HIV), such as a human with AIDS, with the purina nucleotides 2',3'-dideoxy-2'-beta-fluoroadenosine (FddA) and 2',3'-dideoxy-2'-beta-fluoroinosine (FddI) are disclosed. These nucleotides are stable in an acid environment and thus can be used for oral administration. Methods of inhibiting human immunodeficiency virus replication in a human T cell using these purina nucleotides are also disclosed.

2',3'-dideoxy-2'-fluoro-purine nucleosides and methods for using same

Purine nucleosides active against human immunodeficiency virus which are substituted at the 2'-position by a strong electronegative group such as fluorine are stable in an acid environment and thus can be used for oral administration.

Acid stable purine dideoxynucleosides

The present invention relates, in general, to prodrugs. In particular, the present invention relates to lipophilic, aminohydrolase-activated, anti-viral nucleoside prodrug compounds, pharmaceutical compositions containing these compounds, and methods of using these compounds.

Lipophilic, aminohydrolase-activated prodrugs

5-substituted 2',3'-dideoxycytidine compounds and their monophosphates are disclosed which have been found to have potent activity against retroviruses. The 5-fluoro-and 5-aza-substituted 2',3'-dideoycytidine compounds have been found to be effective against HTLV-III/LAV virus.

5-substituted-2',3'-dideoxycytidine compounds with anti-HTLV-III activity

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Silver Spring, MD, United States of America

James A Kelley