The present invention provides an immunoconjugate having the formula:
T-c-E.sub.n-c-Fc.sub.n or T-c-Fc.sub.n-c-E.sub.n;
wherein, T is a single chain variable portion fragment of a monoclonal antibody (scFv) directed to a target protein, polypeptide, or fragment thereof, which is highly expressed on cancer cells; E is two or more foreign immunogenic CD8.sup.+ T cell antigenic epitopes; c is a peptide or polypeptide fragment thereof, capable of being cleaved by a specific protease; and Fc is two or more Fc portions of an IgG antibody. Nucleic acid sequences encoding the same and vectors containing said nucleic acid sequences are also provided. Methods of making the immunoconjugate, along with methods of making target cells susceptible to CTL mediated cell killing, and methods for treatment of cancers are also provided.

The presently disclosed inventive concept(s) include inhibitors of antiplasmin cleaving enzyme (APCE) and fibroblast activation protein alpha (FAP) which can be used in various therapies related to disorders of fibrin and .sub.2-antiplasmin and abnormal cell proliferation. The presently disclosed inventive concept(s) also include substrates of APCE and FAP, which may be used, for example, in screening methods for identifying such inhibitors. The presently disclosed inventive concept(s) further include, but are not limited to, methods of treating or inhibiting atherosclerosis and thrombus disorders by altering the ratios of types of plasma .sub.2-antiplasmin and to methods of treating conditions involving abnormal cell proliferation such as cancers.

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant.

The invention provides compounds having the general formula I:

YXZ I

and salts thereof, wherein the variables X, Y, and Z have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant.

Described herein are therapeutic compositions for the treatment of mitochondrial disorders, and in particular mitochondrial disorders of the eye, including age-related macular degeneration (AMD). In particular, described herein are prodrugs of mitochondrial targeted tetrapeptides that have a cleavable covalent bond (e.g., an ester bond) to a conjugation moiety, wherein the conjugation moiety of the prodrug noncovalently complexes with one or more complexation agents to form drug-complex particulates with a defined avidity, and one or more drug-complex particulates are added to and dispersed within a dispersal medium forming a multiphasic colloidal suspension that serves as an extended release drug delivery system for ocular drug delivery. This extended release drug delivery system may be injected or inserted into the eye (e.g., vitreous) to reverse and prevent mitochondrial dysfunction in the eye for one or more months without requiring retreatment.

Inhibitors of fibroblast activation protein alpha (FAP) and Prolyl Oligopeptidase (POP) are disclosed, along with their use in various therapies related to conditions, diseases, and disorders involving abnormal cell proliferation such as malignancies and angiogenesis, and in neural disorders such as Alzheimer's disease. Stalk portions of the inhibitor molecules, and substrates of FAP and POP, are also disclosed and may be used, for example, in screening methods for identifying such inhibitors.

Disclosed are compositions and methods related to improving pharmacological properties of bioactive compounds targeting nervous system.

Provided herein are antibacterial compounds, wherein the compounds in some embodiments have broad spectrum bioactivity. In various embodiments, the compounds act by inhibition of bacterial type 1 signal peptidase (SpsB), an essential protein in bacteria. Pharmaceutical compositions and methods for treatment using the compounds described herein are also provided.

The invention relates to a process for solution-phase synthesis of D-Arginyl-2,6-dimethyl-L-tyrosyl-L-lysyl-L-phenylalaninamide, an active ingredient used for both common and rare diseases including a mitochondrial targeted therapy for ischemia reperfusion injury.