The United States of America As Represented by the Secretary of

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

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

Children's Medical Center Corporation

Frank A Robey

John K Inman

George R Martin

Marjorie Robert-Guroff

Hynda K Kleinman

Wolfgang F Lindner

Subhash Dhawan

Marian R Neutra

Yoshihiko Yamada

Makoto Sasaki

Jeannette O Graf

Andreas Frey

Yukihide Iwamoto

Raymond L Fields

Tracy A Harris-Kelson

The present invention is a spatially aligned conjugated composition which comprises at least one chemically modified substance which is immunologically representative of a prechosen infectious agent and provides a chemical constituent for entering into and forming a thioether bond; a plurality of chemically substituted metallic oxide particles which range from about 10-10,000 nanometers and are able to enter into a thioether bond and covalent linkage; and at least one thioether bond and linkage joining the metallic oxide particles in a controlled and spatially aligned manner to the antigen or hapten. The conjugated composition may be alternatively employed as an immunogen; as a vaccine; as a diagnostic tool and reactant; and as an analytical material suitable for testing the pharmacological activity of new compounds.

Spatially aligned conjugated composition having a thioether bond linkage

The present invention relates to synthetic peptide analogues useful as therapeutic agents, immunogens or for the diagnosis of disease. In particular, it relates to peptide multimers which maintain the conformation of the native proteins from which they are derived. Peptomers constructed from peptides derived from gp120 of the human immunodeficiency virus are exemplified.

Peptomers with enhanced immunogenicity

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.

The present invention is directed to a human serum amyloid P component peptide sequence having 12 ammo acid residues and having the sequence identified as Glu-Lys-Pro-Leu-Gln-Asn-Phe-Thr-Leu-Cys-Phe-Arg. The invention is also directed to fragments of the above peptide. Two fragments useful in the present invention have the sequence Phe-Thr-Leu-Cys-Phe-Arg and Leu-Cys-Phe-Arg. The above peptides are useful for attaching cells to substrates such as ceramics, tissue culture, dishes, polymers or enamels and thus are useful as research tools for studying particular cells. The above peptides are also useful in vivo as artificial organ replacements which attach surrounding natural cells.

Cell attachment peptides derived from amyloid P component

Peptides with laminin activity are provided as follows:

Peptides with laminin activity

A method to incorporate bromoacetyl and chloroacetyl moieties on amino groups of synthetic peptides using a standard program with an automated peptide synthesizer has been developed. The bromoacetyl and chloroacetyl-derivatized peptides react well with sulfhydryl-containing proteins and with peptides containing cysteine residues. Autopolymerization or cyclization occurs by reaction of the free sulfhydryl of cysteine in a peptide with the bromoacetyl group (or chloroacetyl group) and reactions can generally be controlled by controlling the concentrations of starting peptide in neutral pH buffers. Analytical methods for evaluating the polymers or cyclized peptides include gel filtration chromatography, reverse phase HPLC, SDS-PAGE and amino acid analysis where the degree of reaction can be evaluated by quantifying the amount of S-carboxymethylcysteine formed after HCl hydrolysis. N-bromoacetyl-derivatized peptides are useful as reagents for potential peptide immunogens, vaccines and therapeutics, and for substances such as peptides linked to polymers, plastics, enamels, and ceramics.

Growing community of inventors

Bethesda, MD, United States of America

Frank A Robey