Abstract: Compounds, compositions, and methods are provided that are useful in treating brain diseases by effecting delivery across the blood brain barrier of molecules that otherwise do not (or insignificantly) pass across the blood brain barrier, where compounds of the present technology include but are not limited to cyclo(1,6)SHAVSS (“HAVN1”), cyclo(1,5)SHAVS (“HAVN2”), cyclo(1, 8)TPP V SHAV (“cyclic ADTHAV”), cyclo(1,6)ADTPPV (“ADTN1”), cyclo(1,5)DTPPV (“ADTN2”), acetyl-TPPVSHAV-NH2 (“linear ADTHAV”), and pharmaceutically acceptable salts thereof.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A molecular conjugate is provided having the formula: wherein R1 is 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 —O— or —NH—, 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 R2 is —CH?CH(W), —CH(OH)CH(OH)W, or —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.

Abstract: A molecular conjugate is provided having the formula: wherein n is the conjugation number, P is a moiety of a carrier molecule such as a protein, R1 is a moiety of a biologically active molecule or its analogs, derivatives, salts or secondary amines, Z is —O— or —NH—, and Y is a straight or branched alkyl having 1 to 20 carbons 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, electron-withdrawing or electron-donating groups. Compounds and methods useful in producing such molecular conjugates are also provided, as well as methods of concentrating biologically active molecules in selected target cells of a patient that comprise administering to the patient a selected dose of such molecular conjugates.

Abstract: The invention discloses compositions and methods useful for treating and preventing autoimmune diseases. The compositions and methods utilize peptides that are cell-specific. The peptides are conjugated to drugs. The peptide-drug conjugate can be internalized by the targeted cells thereby allowing for cell-specific delivery of the drug.

Abstract: A molecular conjugate is provided having the formula: 1

Abstract: 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.

Abstract: 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.

Abstract: 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.