Abstract: Novel compounds (small molecules) that potently and selectively inhibit MMP-13 (i.e., MMP-13 inhibitors) are used for treatment of multiple myeloma. The MMP-13 inhibitors described herein are highly selective for MMP-13 and when administered to an individual in need thereof, the compounds selectively kill multiple myeloma cells, reduce growth of multiple myeloma cells, inhibit multiple myeloma-induced osteoclastogenesis, and increase survival time in the individual.

Abstract: The invention provides methods for treating cancers, such as melanoma and/or metastatic melanoma, using compounds that interact with and/or inhibit cellular proteins lamin A/C, ATP-dependent RNA helicase DDX1 (DDX1), heterogeneous nuclear ribonuclear protein H1/H2 (hnRNP H2), and/or heterogeneous nuclear ribonuclear protein A2/B1 (hnRNP A2/B1). The invention additionally provides a method for identifying compounds active against melanoma cells.

Abstract: We describe the use of comparative structural analysis and structure-guided molecular design to develop potent and selective inhibitors (10d and (S)-17b) of matrix metalloproteinase 13 (MMP-13). We applied a three-step process, starting with a comparative analysis of the X-ray crystallographic structure of compound 5 in complex with MMP-13 with published structures of known MMP-13 inhibitor complexes followed by molecular design and synthesis of potent, but non-selective zinc-chelating MMP inhibitors (e.g., 10a and 10b). After demonstrating that the pharmacophores of the chelating inhibitors (S)-10a, (R)-10a, and 10b were binding within the MMP-13 active site, the Zn2+ chelating unit was replaced with non-chelating polar residues that bridged over the Zn2+ binding site and reach into a solvent accessible area.

Abstract: The invention provides methods for treating cancers, such as melanoma and/or metastatic melanoma, using compounds that interact with and/or inhibit cellular proteins lamin A/C, ATP-dependent RNA helicase DDX1 (DDX1), heterogeneous nuclear ribonuclear protein H1/H2 (hnRNP H2), and/or heterogeneous nuclear ribonuclear protein A2/B1 (hnRNP A2/B1). The invention additionally provides a method for identifying compounds active against melanoma cells.

Abstract: Matrix metalloproteinases (MMPs) compositions, inactive forms of MMPs (e.g. proMMPs), fragments, mutants, variants or combinations thereof. A pharmaceutical composition comprises one or more of the above in a pharmaceutical carrier. A composition comprises at least one of: a matrix metalloproteinase (MMP), an inactive MMP or a proenzyme (proMMP) thereof, wherein the matrix metalloproteinase (MMPs), inactive MMPs or proMMPs thereof, comprise: MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-11, MMP-12, MMP-13.MMP-14, MMP-15, MMP-16, MMP-17, MMP-18, MMP-19, MMP-20, MMP-21, MMP-23A, MMP-23B, MMP-24, MMP-25, MMP-26, MMP-27, MMP-28, active fragments, mutants, variants or any combinations thereof. The uses include isolation of cells, in particular stem cells, from tissues, dissociation of tissues, proteins and treatment of a variety of conditions.

Abstract: Isolation, synthesis and therapeutic use of conotoxin and conophan compounds and related compositions including a new class of conopeptides including the modified amino acid D-?-hydro-oxyvalinie (D-Hyv=V*) are described herein. These isolated peptides are the first known example of a naturally occurring polypeptide chain containing D-Hyv. The active peptides, termed ?-Hydroxyconophans are heavily hydroxylated small peptides. These peptides contain a definitive structural motif which is a double modification of the polypeptide chain (?-D-OH-Hyv-Trp).

Abstract: Synthetic triple-helical peptides (THPs) are used for the design and synthesis of triple-helical transition state analog inhibitors. These inhibitors feature a phosphonate ester or phosphinic moiety in place of the scissle bond. These groups inhibit MMPs, and methods been developed for their convenient incorporation within a peptide sequence by solid-phase methods.

Abstract: Disclosed are methods and compositions for modulation of ion levels in cells. The compositions contain a new class of biologically active peptides derived from the venom of predatory marine snails of the species Conus gladiator and Conus mus. The active peptides, termed &ggr;-Hydroxyconophans are heavily hydroxylated small peptides. These peptides contain a definitive structural motif which is a double modification of the polypeptide chain in contiguous residues, i.e., &ggr;-OH-Hyv-D-Trp.

Abstract: A peptide-amphiphile complex having a lipophilic portion and a peptide portion, wherein the peptide portion has a secondary structure.

Abstract: A method for making a medical device having a biomolecule immobilized on a substrate surface is provided. The method includes: providing an immobilized biomolecule comprising a biomolecule covalently attached to a support material; attaching a photoreactive crosslinking agent to the immobilized biomolecule to form a photoreactive analog of the biomolecule; and removing the photoreactive analog of the biomolecule from the support material. The photoreactive analog of the biomolecule can then be attached to a substrate surface, such as a biomaterial that forms part of a medical device. The immobilized biomolecule may contain a peptide having an N.sup..alpha. -terminus. The photoreactive crosslinking agent is attached to the peptide at the N.sup..alpha. -terminus to form the photoreactive analog of the biomolecule. The peptide can be an adhesion peptide containing the sequence Trp-Gln-Pro-Pro-Arg-Ala-Arg-Ile. Attachment of the peptide to a substrate surface promotes cell adhesion to the surface.

Abstract: A method of screening a sample for the presence of a matrix metalloproteinase employing discriminatory peptide substrates is provided. The method involves providing a peptide substrate of 6-14 amino acid residues containing at least one matrix metalloproteinase cleavage site. The peptide substrate contains Mca as a fluorogenic group and Lys(Dnp) as a quenching group separated by at least four amino acid residues, wherein the peptide substrate is specific for the matrix metalloproteinase of interest. The peptide substrate is combined with a sample containing at least one matrix metalloproteinase to form a mixture. The fluorescence of the mixture is monitored to determine if the matrix metalloproteinase of interest is present.

Abstract: Polypeptides are provided that have a sequence of at least about four amino acids corresponding substantially to an amino acid sequence within the triple-helical domain of Type I collagen. The polypeptides promote cell adhesion and/or cell migration. Cell culture substrates coated with the polypeptides are also provided. Prosthetic devices and methods for identifying and distinguishing cells of different types are also provided.

Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.

Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.