National Institutes of Health, a Component of the US Dept. of Health & Human Services

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

Other

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

Government of the United States

John K Inman

Ettore Appella

William G Rice

Frank A Robey

Mingjun Huang

Atul Goel

David Covell

James A Turpin

Yongsheng Song

Anders Wallqvist

Andrew Maynard

Jim A Turpin

Marco Schito

David D Roberts

Henry C Krutzsch

Joseph L Bryant

Nenghua Guo

Philip J Browning

Schito Marco

Certain thiol and acylthiol compounds inhibit retrovirus growth by attacking the highly conserved zinc finger regions of essential viral proteins. These compounds, compositions containing them, and methods of using them to treat retroviral infections such as HIV are described. These compounds are also useful for preparation of vaccines comprised of inactivated retroviruses such as HIV, prevention of the transmission of such retroviruses, and detection of retroviral proteins.

Acythiols and component thiol compositions as anti-HIV and anti-retroviral agents

This invention pertains to the discovery of a novel family of thiolesters and uses thereof. Also provided for are viricidal compounds and pharmaceutical formulations comprising these novel thiolesters. The invention also provides thiolester-inactivated viruses and thiolester-complexed viral proteins.

Thiolesters and uses thereof

Acylthiols and component thiol compositions as anti-HIV and anti-retroviral agents

This invention identifies a biologically active group of peptide sequences from Type I repeat units of the extracellular matrix protein, human thrombospondin-1, identical or homologous to the sequence, KRFKQDGGWSHWSPWSSC (SEQ ID NO:30). The biological activities residing with the full sequences, portions thereof, and variants of the full or partial sequences are disclosed. The invention describes how biological activity may be enhanced by covalently linking these peptides to suitable carriers, preferably a branched, water-soluble polymer of low (or absent) toxicity and immunogenicity, such as polysucrose (Ficoll.TM.). The invention describes (1) a method for preparing such conjugates, (2) the use of the defined peptides or their conjugates in blocking or modifying the action on cellular processes of heparin (e.g., proliferation, adhesion, motility, extravasation and neovascularization), sulfatides, related sulfated glycoconjugates, fibronectin, and basic fibroblast growth factor, involving malignant cell lines and normal endothelial cells. Use of the defined peptides, analogs or peptidomimetics and their conjugates for treatment of metastatic tumors, breast carcinomas, melanomas, Kaposi's sarcomas, hemangiomas, diabetic retinopathies, and various pathological conditions dependent upon neovascularization is also disclosed.

Heparin- and sulfatide binding peptides from the type I repeats of human

A new amino acid derivative, N.sup..alpha. -tert-butoxycarbonyl-N.sup.e -(N-bromoacetyl-.beta.-alanyl)-L-lysine (BBAL), has been synthesized as a reagent to be used in solid-phase peptide synthesis for introducing a side-chain bromoacetyl group at any desired position in a peptide sequence. The bromoacetyl group subsequently serves as a sulfhydryl-selective cross-linking function for the preparation of cyclic peptides, peptide conjugates and polymers. BBAL residues are stable to final HF deprotection/cleavage. BBAL peptides can be directly coupled to other molecules or surfaces which possess free sulfhydryl groups by forming stable thioether linkages. Peptides containing both BBAL and cysteine residues can be self-coupled to produce either cyclic molecules or linear peptide polymers. Such peptide derivatives are useful in preparing potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels and ceramics.

Amino acid derivative and bromoacetyl modified peptides for the

A new amino derivative, N.sup..alpha. -tert-butoxycarbonyl-N.sup..epsilon. -(N-bromoacetyl-.beta.-alanyl)-L-lysine (BBAL), has been synthesized as a reagent to be used in solid-phase peptide synthesis for introducing a side-chain bromoacetyl group at any desired position in a peptide sequence. The bromoacetyl group subsequently serves as a sulfhydryl-selective cross-linking function for the preparation of cyclic peptides, peptide conjugates and polymers. BBAL residues are stable to final HF deprotection/cleavage. BBAL peptides can be directly coupled to other molecules or surfaces which possess free sulfhydryl groups by forming stable thioether linkages. Peptides containing both BBAL and cysteine residues can be self-coupled to produce either cyclic molecules or linear peptide polymers. Such peptide derivatives are useful in preparing potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels and ceramics.

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Bethesda, MD, United States of America

John K Inman