Abstract: The present invention provides methods of synthesizing a molecule comprising a functional moiety which is operatively linked to an encoding oligonucleotide. The methods include providing an initiator compound comprising an initial functional moiety comprising n building blocks, wherein the initial functional moiety comprises at least one reactive group, and is operatively linked to an initial oligonucleotide; reacting the initiator compound with a building block comprising at least one complementary reactive group, under conditions suitable for reaction of the complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide with an incoming oligonucleotide corresponding to the building block in the presence of an enzyme which catalyzes ligation of the initial oligonucleotide and the incoming oligonucleotide, under conditions suitable for ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide.

Abstract: The present invention provides methods of synthesizing libraries of molecules comprising a functional moiety which is operatively linked to an encoding oligonucleotide.

Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural ? amyloid peptides (?-AP). In a preferred embodiment, the ? amyloid modulator compounds of the invention are comprised of an A? aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural ? amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural ?-AP aggregation when the natural ?-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Abstract: Compounds that modulate natural ? amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a ? amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a ? amyloid peptide, preferably a retro-inverso isomer of A?17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an acetate group, an alkyl amide group, an aryl amide group or a hydroxy group.

Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural ? amyloid peptides (?-AP). In a preferred embodiment, the ? amyloid modulator compounds of the invention are comprised of an A? aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural ? amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural ?-AP aggregation when the natural ?-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Abstract: The present invention provides methods of parasitic infections, thymoma, and lymphoid malignancies in a subject by administering to the subject a therapeutically effective amount of one or more of the compounds of the invention.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: The present invention provides methods and compositions for treating inflammatory disorders, e.g., asthma, lung inflammation or cancer.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptidic compound (e.g., a peptide, polypeptide, protein, peptidomimetic or the like) and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptidic compound in a small volume and for delivery of a pharmaceutically active peptidic compound for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptidic compound of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.

Abstract: Sustained delivery formulations comprising a water-insoluble complex of a peptidic compound (e.g., a peptide, polypeptide, protein, peptidomimetic or the like) and a carrier macromolecule are disclosed. The formulations of the invention allow for loading of high concentrations of peptidic compound in a small volume and for delivery of a pharmaceutically active peptidic compound for prolonged periods, e.g., one month, after administration of the complex. The complexes of the invention can be milled or crushed to a fine powder. In powdered form, the complexes form stable aqueous suspensions and dispersions, suitable for injection. In a preferred embodiment, the peptidic compound of the complex is an LHRH analogue, preferably an LHRH antagonist, and the carrier macromolecule is an anionic polymer, preferably carboxymethylcellulose. Methods of making the complexes of the invention, and methods of using LHRH-analogue-containing complexes to treat conditions treatable with an LHRH analogue, are also disclosed.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of inducing an immunosupressed condition and/or treating chronic allograft vasculopathy in a subject undergoing or who has undergone a transplant, by administering to the subject a therapeutically effective amount of one or more of the compounds of the invention.

Abstract: The present invention relates to compounds which modulate the activity of the S1P1 receptor, the use of these compounds for treating conditions associated with signaling through the S1P1 receptor, and pharmaceutical compositions comprising these compounds.

Abstract: The present invention provides angiogenesis inhibitor compounds comprising a MetAP-2 inhibitory core coupled to a peptide, as well as pharmaceutical compositions comprising the angiogenesis inhibitor compounds and a pharmaceutically acceptable carrier. The present invention also provides methods of treating an angiogenic disease, e.g., cancer, in a subject by administering to the subject a therapeutically effective amount of one or more of the angiogenesis inhibitor compounds of the invention.

Abstract: Methods for treating hormone associated conditions, such as endometriosis, uterine leiomata, ovarian cancer, breast cancer, or vaginal bleeding, using LHRH antagonists and selective estrogen receptor modulators are disclosed. The methods include administering to a subject a combination of an LHRH antagonist and a selective estrogen receptor modulator. Pharmaceutical compositions and kits for use in the methods of the invention are also provided.

Abstract: The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

Abstract: Compounds that modulate natural ? amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a ? amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3–5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a ? amyloid peptide, preferably a retro-inverso isomer of A?17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group.

Abstract: Methods for treating FSH related conditions, such as prostatic intraepithelial neoplasia, pedophilia, infertility, or vaginal bleeding, with GnRH antagonists are disclosed. The methods of the invention generally feature administering to a subject a GnRH antagonist suitable for in vivo administration and able to reduce both plasma FSH and LH levels in a subject, in an amount or in a formulation effective to reduce plasma FSH levels in the subject to a symptom alleviating level. In vitro fertilization and male contraceptive methods are also provided.

Abstract: The present invention provides methods of parasitic infections, thymoma, and lymphoid malignancies in a subject by administering to the subject a therapeutically effective amount of one or more of the compounds of the invention.

Abstract: The present invention provides methods of treating an autoimmune disorder (e.g., lupus erythematosus, multiple sclerosis, myasthenia gravis, vasculitis and diabetes mellitus) in a subject by administering to the subject a therapeutically effective amount of one or more compounds of the invention.