A modified Ac-TMP-2 protein lacks one or a plurality of acidic C-terminal amino acids normally present in a full-length or wild-type Ac-TMP-2 protein and may also lack one or a plurality of N-terminal amino acids while retaining the amino acid sequence C-S-C at or near the N-terminus. The modified Ac-TMP-2 protein may be useful in method and composition for reducing or alleviating inflammation in a subject. Inflammation may be associated with a disease is a disease of the digestive tract such as chronic gastritis or an inflammatory bowel disease such as Crohn's disease or ulcerative colitis, or a disease of the respiratory system, such as asthma, emphysema, chronic bronchitis, and chronic obstructive pulmonary disease.

Provided are compositions and methods for inhibiting extracellular matrix metalloproteinase-2 (MMP-2) activity. Inhibition of extracellular MMP-2 activity can be useful for restricting extracellular matrix remodeling, tumor cell migration, cell invasion, and/or metastasis. The compositions comprise mutants of Tissue Inhibitor of Metalloproteinase-2 (TIMP-2), where the tyrosine at position 62, 90 and/or 165 has been substituted with a non-phosphorylatable amino acid or with a phosphomimetic of phosphorylated tyrosine, and/or anti-Src antibodies. The method comprises delivering to an extracellular region of a tissue, a composition comprising a TIMP-2 mutant and/or an anti-Src antibody.

A composition comprising as components a polypeptide IMPI (including wild type) and/or a polypeptide IMPI-fusion and at least one antibiotic compound, in particular an aminoglycoside antibiotic, and/or at least one bactericidal compound, wherein the polypeptides, the at least one antibiotic and the at least one bactericidal compound is present in the composition in concentrations which exhibit in combination a synergistic effect against resistant bacteria.

There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

The invention discloses a multi-functional fusion polypeptide and its preparation method and application thereof, in the field of biopharmaceutics. The fusion polypeptide of the present invention comprises the domain Pro-(D-Pyr)-(D-Cys)-Bip-Arg-Gly-Glu, Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro, Arg-Gly-Asp, and Gly-Gly-Gly-Gly, and can treat human pulmonary fibrosis, lung tissue lesions, lung cancer and other tumors. In a cell model for pulmonary fibrosis, the polypeptide of the present invention can significantly lower the hydroxyproline content and suppress the progression of pulmonary fibrosis. MTT assay shows that the polypeptide of the present invention can inhibit the proliferation multiple human tumor cells. The polypeptide of the present invention is prepared by a synthetic method that is uncomplicated method and offers good application prospects.

There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

Peptide-immuno-oncology agent complexes (peptide-I/O complexes) that can home, target, migrate to, are directed to, are retained by, accumulate in, penetrate, or bind to the tumor microenvironment, tumor tissues, or cells or compartments or cytosol of cells thereof, or any combination thereof, are disclosed. Additionally disclosed are peptide-I/O complexes that can cross the blood-brain barrier. Pharmaceutical compositions and uses for peptide-I/O complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of an immuno-oncology agent (I/O) to the tumor microenvironment. Targeted compositions of the disclosure can deliver peptide-I/O complexes to target regions, tissues, structures or cells targeted by the peptide.

The present invention provides compounds for disrupting the binding of a matrix metalloprotease (MMP) protein to a substrate protein at an interaction site other than the protease catalytic site. In particular the inventive compounds inhibit the MMP's ability to cleave a substrate protein. In some cases the compound may prevent activation of transforming growth factor beta (TGF). The compounds are preferably polypeptide fragments of the hemopexin-like domain of the MMP, but may be mimetics thereof or peptides or mimetics of the portion of the MMP substrate protein to which the MMP interacts.

The application concerns tissue inhibitor of metalloproteinase 3 (TIMP-3) muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them; in particular, muteins of TIMP-3 with specific amino acid substitutions in order to introduce N-linked glycosylation sites.

A modified Ac-TMP-2 protein lacks one or a plurality of acidic C-terminal amino acids normally present in a full-length or wild-type Ac-TMP-2 protein and may also lack one or a plurality of N-terminal amino acids while retaining the amino acid sequence C-S-C at or near the N-terminus. The modified Ac-TMP-2 protein may be useful in method and composition for reducing or alleviating inflammation in a subject. Inflammation may be associated with a disease is a disease of the digestive tract such as chronic gastritis or an inflammatory bowel disease such as Crohn's disease or ulcerative colitis, or a disease of the respiratory system, such as asthma, emphysema, chronic bronchitis, and chronic obstructive pulmonary disease.