A method of treatment of inflamed, pre-cancerous or cancerous tissue or polyps in a mammalian subject is disclosed. The treatment involves administration of a composition of at least one peptide agonist of a guanylate cyclase receptor and/or other small molecules that enhance intracellular production of cGMP. The at least one peptide agonist of a guanylate cyclase receptor may be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The inhibitor may be a small molecule, peptide, protein or other compound that inhibits the degradation of cGMP. Without requiring a particular mechanism of action, this treatment may restore a healthy balance between proliferation and apoptosis in the subject's population of epithelial cells, and also suppress carcinogenesis. Thus, the method may be used to treat, inter alia, inflammation, including gastrointestinal inflammatory disorders, general organ inflammation and asthma, and carcinogenesis of the lung, gastrointestinal tract, bladder, testis, prostate and pancreas, or polyps.

The present invention provides peptides of general formula (I) and salts thereof, wherein: R.sub.1 and R.sub.2, taken together, form a birradical linker; and R.sub.2 is hydrogen; or, alternatively, R.sub.1 is selected from hydrogen, C(O)CH.sub.2NHC(O)(C.sub.1-C.sub.5)alkyl, and C(O)(C.sub.1-C.sub.20)alkyl; one of R.sub.2 and R.sub.2 is hydrogen and the other is selected from C(O)NR.sub.3R.sub.4, and C(O)OH; and R.sub.3 and R.sub.4 are same or different and are selected from hydrogen and (C.sub.1-C.sub.10)alkyl. These peptides are highly efficient in binding and inhibiting FoxP3, being efficient in inhibiting and blocking Treg cell functionality, which make them useful in the treatment of cancer. The present invention also provides constructs comprising the peptide of formula (I) as well as combinations comprising the peptide of formula (I), the construct or both.

##STR00001##

The present invention provides peptides of general formula (I) and salts thereof, wherein: R.sub.1 and R.sub.2, taken together, form a birradical linker; and R.sub.2 is hydrogen; or, alternatively, R.sub.1 is selected from hydrogen, C(O)CH.sub.2NHC(O)(C.sub.1-C.sub.5)alkyl, and C(O)(C.sub.1-C.sub.20)alkyl; one of R.sub.2 and R.sub.2 is hydrogen and the other is selected from C(O)NR.sub.3R.sub.4, and C(O)OH; and R.sub.3 and R.sub.4 are same or different and are selected from hydrogen and (C.sub.1-C.sub.10)alkyl. These peptides are highly efficient in binding and inhibiting FoxP3, being efficient in inhibiting and blocking Treg cell functionality, which make them useful in the treatment of cancer. The present invention also provides constructs comprising the peptide of formula (I) as well as combinations comprising the peptide of formula (I), the construct or both.

##STR00001##

The disclosure relates to methods of prophylactic and therapeutic treatments of a Pneumocystis infection (i.e., an infection caused by Pneumocystis jirovecii) in a subject by administering to the subject a compound of any of formulas (I)-(III) (e.g., a salt of Compound 1, or a neutral form thereof). The disclosure also relates to methods of inhibiting the replication of a Pneumocystis spp. The methods of the disclosure can be useful in immunocompromised subjects.

The disclosure relates to methods of prophylactic and therapeutic treatments of a Pneumocystis infection (i.e., an infection caused by Pneumocystis jirovecii) in a subject by administering to the subject a compound of any of formulas (I)-(III) (e.g., a salt of Compound 1, or a neutral form thereof). The disclosure also relates to methods of inhibiting the replication of a Pneumocystis spp. The methods of the disclosure can be useful in immunocompromised subjects.

The present disclosure provides a large combinatorial library of cell-permeable bicyclic peptides. The bicyclic peptides described herein include the first ring consisted of randomized peptide sequences for potential binding to a target of interest while the second ring featured a family of different cell-penetrating motifs, for both cell penetration and target binding. The library was screened against the IB kinase / (IKK/)-binding domain of NF-kB essential modulator (NEMO), resulting in the discovery of several cell-permeable bicyclic peptides which inhibited the NEMO-IKKb interaction, thereby selectively inhibiting canonical NF-kB signaling in mammalian cells and the proliferation of cisplatin-resistant ovarian cancer cells.

The present invention relates to methods for displaying cyclic peptides on the surface of bacteriophage particles and collections thereof.

The present invention relates to methods for displaying cyclic peptides on the surface of bacteriophage particles and collections thereof.

The present invention provides compounds, compositions thereof, and methods of using the same.

The present invention provides compounds, compositions thereof, and methods of using the same.