University of Kansas

Tapestry Pharmaceuticals, Inc.

Sanofi Pharmaceuticals, Inc.

Teruna J Siahaan

Stephen H Benedict

Marcia A Chan

Scott A Tibbetts

Cory Berkland

James D McChesney

Madhavi C Chander

Christine R Xu

Sterling K Ainsworth

Valentino J Stella

Lawrence I Kruse

Thomas D Gordon

Binghe Wang

Mark A Ator

Ronald T Borchardt

Karthik Ramachandran

Lisa Stehno-Bittel

Joshua Sestak

Naoki Kobayashi

Joseph S Murray

Prakash Manikwar

Yongbo Hu

Paul Kipkemboi Kiptoo

Ahmed Badawi

Barlas Buyuktimkin

Iwao Nozawa

John M Stewart

Sanjeev Gangwar

James Arthur Gainor

Barry Arnold Morgan

Bifunctional conjugate compositions are provided comprising a Signal-1 moiety bound to a first polymer carrier, wherein the combined size of the Signal-1 moiety and the first polymer carrier is about 1 nanometer to about 500 nanometers; and a Signal-2 moiety bound to a second polymer carrier, wherein the combined size of the Signal-2 moiety and the second polymer carrier is about 1 nanometer to about 500 nanometers. In some embodiments, the Signal-1 moiety and the Signal-2 moiety are bound to the same polymer carrier. Associated methods are also provided.

Bifunctional conjugate compositions and associated methods

The present disclosure provides IDAC compounds capable of presenting two or more signal 1 moieties to a host immune system and methods of using the IDAC compounds to treat or prevent autoimmune disorders in a subject. The present disclosure provides compounds including a modified I-domain peptide having two or more modified lysine residues and two or more signal 1 moieities conjugated to the modified lysine residues of the I-domain peptide and methods of using an making the compounds.

Compositions including I-domain antigen conjugate compounds and methods for treatment of autoimmune disorders

A scaffold having islet cells or small islet cell clusters attached thereto in a multilayer, and a micro-mold having divots for culturing islets, wherein islet formation is influenced by the shape and dimensions of the divots are disclosed.

Templated islet cells and small islet cell clusters for diabetes treatment

Novel bifunctional peptides useful in the treatment and/or diagnosis of EAE or MS. The peptides have a first peptide portion derived from an epitope of myelin proteolipid protein, myelin oligodendrocyte glycoprotein, or oligodendrocyte-specific peptide and a second peptide portion derived from CD11a (LFA-1 alpha subunit), CD18 (LFA-1 beta subunit), CD154 (CD40L), Fas-Ligand, or CTLA4. The carboxy and/or amino termini of the bifunctional peptides may be modified.

Bi-functional peptides for multiple sclerosis treatment and diagnosis

A novel peptide sequence having the general formula AB wherein each of A and B represent a chain of amino acid residues and wherein said A chain is capable of binding with a major histocompatibility complex on an antigen presenting cell, and wherein said B chain is capable of binding with a Signal-2 receptor on an antigen presenting cell. Preferred forms of the peptide sequence further include an X chain positioned intermediate the A chain and the B chain. Moreover, preferred forms include an A chain which has at least about 10% sequence homology with a Signal-1 moiety, or is a peptidomimetic of a Signal-1 moiety, said B chain has at least 10% sequence homology with a Signal-2 receptor moiety, or is a peptidomimetic of a Signal-2 receptor moiety, and wherein the X chain has at least one amino acid residue, or is a peptidomimetic of that amino acid residue. Advantageously, the novel peptide sequence is capable of shifting a type-1 immune response to a type-2 immune response or from a type-2 immune response to a type-1 immune response.

Signal-1/signal-2 bifunctional peptide inhibitors

A molecular conjugate is provided having the formula: wherein Ris a de-hydroxyl or de-amino moiety respectively of a hydroxyl-bearing or amino-bearing biologically active molecule or an analog or derivative thereof, and Z is &#x2014;O&#x2014; or &#x2014;NH&#x2014;, respectively, Y is a straight or branched alkyl having 1 to 20 carbons that may be optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl groups, electron-withdrawing groups, or electron-donating groups; and Ris &#x2014;CH&#x2550;CH(W), &#x2014;CH(OH)CH(OH)W, or &#x2014;C(O)H, where W can be H, a straight or branched alkyl having 1 to 20 carbons that may be optionally substituted with one or more phenyl, a cycloalkyl optionally substituted with one or more alkyl or phenyl, or an aromatic group optionally substituted with one or more alkyl groups, electron-withdrawing groups, or electron-donating groups.

Molecular conjugates for use in treatment of cancer

Methods and compositions useful in inhibiting integrin-associated diseases are provided. The compositions contain a polypeptide having one or more D-amino acids that inhibit integrin binding to its associated binding polypeptide. The compositions include retro-inverso polypeptides.

D-form polypeptide that inhibits the interaction between LFA-1 and ICAM-1

Peptide compositions which inhibit the binding of one protein to another protein, and corresponding methods of use are disclosed. These peptide compositions include at least one peptide which binds to one protein, and at least one peptide which binds to the other protein. In the preferred embodiment, the peptide composition is composed of a combination of cyclic ICAM-1-based and LFA-1-based peptides which inhibit the binding of LFA-1 to ICAM-1. Such LFA-1/ICAM-1-based peptide compositions can be used to treat disease states such as rejection of transplanted organs, allergies, and autoimmune diseases.

Peptide compositions which induce immune tolerance and methods of use

Peptides or peptides having an amino acid-like moiety in place of an amino acid moiety thereof immobilized on glass beads, especially controlled-pore glass beads, by a C-terminal .alpha.-carboxyl-.omega.-amino linker and .alpha.-silyl-.omega.-amino anchor, especially wherein the anchor has the structural formula

N-terminal-marked peptides immobilized on glass beads and method of

Short-chain peptides replicating fragments of functional domains derived from LFA-1 and ICAM-1 parent protein sequences serve to modulate the ICAM/LFA binding interaction. In one aspect of the invention, this modulation serves to block interprotein binding reactivity, as a peptide of the invention binds to a target protein in a manner that precludes the normal binding reaction between ICAM-1 and LFA-1. In another aspect of the invention, this modulation enhances the reactivity of a first peptide, as a second peptide induces a conformational change in the target protein from a first conformation to a second, more reactive, conformation. The peptides are used according to a method including the steps of providing the proteins and applying them to a population of cells.

ICAM-1/LFA-1 short-chain peptides and method of using same

Provided are cyclic prodrugs of biologically active peptides and peptide nucleic acids exhibiting improved cell membrane permeability and enzymatic stability, containing 3-(2'-hydroxy-4',6'-dimethyl phenyl)-3,3-dimethyl propionic acid and its deriveatives and acyloxyalkoxy linkers. Also provided are pharmaceutical compositions containing effective amounts of these cyclic prodrugs in combination with pharmaceutically acceptable carriers, excipients, or diluents.

Cyclic prodrugs of peptides and peptide nucleic acids having improved

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Lawrence, KS, United States of America

Teruna J Siahaan