Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention relates to compositions which inhibit the binding of nerve growth factor to the p75NTR common neurotrophin receptor and methods of use thereof. In one embodiment, the compound which inhibits binding of nerve growth factor to p75NTR comprises, particularly when bound to nerve growth factor, at least two of the following: (1) a first electronegative atom or functional group positioned to interact with Lys34 of nerve growth factor; (2) a second electronegative atom or functional group positioned to interact with Lys95 of nerve growth factor; (3) a third electronegative atom or functional group positioned to interact with Lys88 of nerve growth factor; (4) a fourth electronegative atom or functional group positioned to interact with Lys32 of nerve growth factor; and (5) a hydrophobic moiety which interacts with the hydrophobic region formed by Ile31, Phe101 and Phe86 of nerve growth factor.

Abstract: The present invention provides methods and compositions for enhancing the effect of a neurotrophin on a cell expressing a neurotrophin receptor. The effect is preferably neurotrophin-mediated growth and/or survival, such as neurite growth. The invention employees amphipathic compounds having a hydrophobic membrane-associating face and a hydrophilic face opposed thereto, which preferably mimic the amphipathic domain of the common neurotrophin receptor p75 from amino acid residue 367 to residue 379. Such compounds have charged moieties, polar moieties or combinations that mimic the charged and polar group relationships of p75NTR367-379, and include but are not limited to peptide analogues thereof. The hydrophobic membrane-associating face can interact with a membrane-bound neurotrophin receptor, such as TrkA, and the opposing hydrophillic face can interact with a DNA binding protein, such as nuclear transcription factor NFkB.

Abstract: Factors and methods for disrupting or inhibiting the association of protomers of a multimeric protein are described. Such inhibition reduces the biological disorders. Particularly, novel neurotrophin antagonists are described. Generally, the antagonist comprises amino acids from positions 68-58 and 108-110 of a neurotrophin, in which the amino acid from position 68 is covalently bound to the amino acid from position 108 and the amino acid from position 58 is covalently bound to the amino acid at position 110 to form a bicyclic structure, in another aspect of the invention transition metal ions are provided for selectively altering the geometry of the receptor binding domains of neurotrophins which allows functionality and activity of the neurotrophins to be selectively reduced. For example Zn2+ alters the conformation of NGF rendering it unable to bind to p75NTR or TrkA receptors or to activate signal transduction and biological outcomes normally induced by this protein.

Abstract: The present invention relates to computational methods for identifying the bioactive conformations of peptide domains, in particular the geometries of complexes of neurotrophins and neurotrophin receptors, and the geometries of neurotrophin receptors and ligands. The invention includes a method for identifying and theoretically modelling a receptor binding site for neurotrophins, such as NGF, BDNF, NT-3 and NT4/5, of the common neurotrophin receptor p75.sup.NTR. The principal residues of the p75.sup.NTR binding site are Asp.sup.47p, Lys.sup.56p, Asp.sup.75p, Asp.sup.76p, Asp.sup.88p and Glu.sup.88p of the second and third cysteine-rich domains. These residues interact with residues of variable loop regions I and V and other neighboring residues of each of the neurotrophins. The invention provides a method of designing a ligand for binding with common neurotrophin receptor p75.sup.

Abstract: Nerve process growth modulation can be achieved using derivatized cyclodextrins. Processes for making sulfated and aminated .beta.-cyclodextrin derivatives are also described in which a compound of the formula R".sub.2 NCH X'.sup.+ X'.sup.- where R.sup.- is an alkyl containing 1-5 carbon atoms and X is selected from bromine and iodine is used to halogenate the cydodextrin.