The Scripps Research Institute

Other

Carlos F Barbas

Richard A Lerner

Angray Singh Kang

Guofu Zhong

Benjamin List

Dennis R Burton

Christoph Rader

Stephen William Santoro

Gerald F Joyce

Brian M Lamb

Doron Shabat

Andrew Mercer

Thomas Gaj

Junho Chung

Subhash C Sinha

Sakthivel Kandasamy

Sakthiel Kandasamy

Jenho Chung

The present invention provides integrin &#x3b1;&#x3b2;specific antibodies and peptides. The antibodies and peptides demonstrate little or no immunoreactivity with other integrins. Methods for inhibiting platelet aggregation using the antibodies and peptides are also provided.

[object Object]

Filamentous phage comprising a matrix of cpvIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a filamentous phage coat protein membrane anchor domain fused to at least one of the polypeptides.

Heterodimeric receptor libraries using phagemids

Catalytic antibodies, including 38C2 and 33F12, are capable of efficiently catalyzing a wide variety of ketone-ketone, ketone-aldehyde, aldehyde-ketone, and aldehyde-aldehyde intermolecular aldol reactions, and in some cases to catalyze their subsequent dehydration to yield aldol condensation products. A number of intramolecular aldol reactions have also been defined. Catalysis of all intramolecular aldol reactions examined yields the corresponding condensation products.

Aldol condensations by catalytic antibodies

Nine efficient aldolase antibodies were generated using hapten 2. This hapten combines, in a single molecule, structural components employed for reactive immunization with structural components employed for forming a transition state analog of the aldol reaction. Characterization of two of these antibodies reveals that they are highly proficient (up to 1000-fold better than any other antibody catalyst) and enantioselective catalysts for aldol and retro-aldol reactions and exhibit enantio- and diastereo-selectivities opposite that of antibody 38C2.

Antibody catalysis of enantio- and diastereo-selective aldol reactions

Three monoclonal aldolase antibodies, generated against a &bgr;-diketone hapten by reactive immunization, catalyzed rapid and highly enantioselective retro-aldol reactions providing ent-9a-k by kinetic resolution. Compounds 9a, 9g and 9k were resolved in multi-gram quantities using 0.005-0.0004 mol % antibody catalyst. Enantiomerically pure starting materials, 9a-k, are useful synthons for the construction of epothilones A-E (2-6) and their analogs including 13-alkyl derivatives. Previously, the use of compound 9a as a synthon was reported in the preparation of epothilones A-D, 2-5. To further expand this synthon-based strategy, syntheses of epothilone E, 6, 13-methyl epothilone C, 7, and their trans-isomers have been achieved starting from enantiomerically pure thiazole aldols 9g and 9a, respectively, prepared by large-scale antibody catalyzed resolutions.

Use of catalytic antibodies for synthesizing epothilone

The present invention provides a compound that includes an active therapeutic agent attached to a blocking moiety that is sensitive to the catalytic action of molecules having retro-aldol and retro-Michael catalytic activity, methods for making such compounds and methods of converting such compounds to active therapeutic agents using molecules having aldolase activity.

Prodrug activation using catalytic antibodies

The present invention describes synthetic human monoclonal antibodies that immunoreact with and neutralize human immunodeficiency virus (HIV). The synthetic monoclonal antibodies of this invention exhibit enhanced binding affinity and neutralization ability to gp120. Also disclosed are immunotherapeutic and diagnostic methods of using the monoclonal antibodies, as well as cell lines for producing the monoclonal antibodies.

Synthetic human neutralizing monoclonal antibodies to human immunodeficiency virus

Filamentous phase comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a filamentous phage coat protein membrane anchor domain fused to at least one of the polypeptides.

Hetrodimeric receptor libraries using phagemids

Nine efficient aldolase antibodies were generated using hapten 2. This hapten combines, in a single molecule, structural components employed for reactive immunization with structural components employed for forming a transition state analog of the aldol reaction. Characterization of two of these antibodies reveals that they are highly proficient (up to 1000-fold better than any other antibody catalyst) and enantioselective catalysts for aldol and retro-aldol reactions and exhibit enantio- and diastereo- selectivities opposite that of antibody 38C2.

Modified pyrimidine nucleotides derivatized at C5 to contain a functional group that mimics the property of a naturally occurring amino acid residues are provided. DNA molecules containing the modified nucleotides are also provided.

Functionalized pyrimidine nucleosides and nucleotides and DNA's incorporating same

Zinc finger-nucleotide binding polypeptides having binding specificity for target nucleotides containing one or GNN triplets are provided. Compositions containing such polypeptides and the use of such polypeptides and compositions for regulating nucleotide function are also provided.

Zinc finger binding domains for GNN

The present invention discloses catalytic or enzymatic DNA molecules that contain a modified nucleotide and that are capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

Enzymatic DNA molecules that contain modified nucleotides

Filamentous phage comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an autogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a cpVIII membrane anchor domain fused to at least on of the polypeptides.

Filamentous phage comprising a matrix of cpVIII proteins encapsulating a genome encoding first and second polypeptides of an antogenously assembling receptor, such as an antibody, and a receptor comprised of the first and second polypeptides surface-integrated into the matrix via a cpVIII membrane anchor domain fused to at least one of the polypeptides with a mutagenized CDR3 region.

Growing community of inventors

Del Mar, CA, United States of America

Carlos F Barbas