Provided is a nRGD polypeptide formed by connecting alanine-alanine-asparagine (AAN) and a polypeptide containing arginine-glycine-aspartic acid (RGD), wherein the nRGD polypeptide can target tumor vessels, tumor cells and tumor-associated macrophages, and mediate the targeted delivery of tumors.

Provided is a nRGD polypeptide formed by connecting alanine-alanine-asparagine (AAN) and a polypeptide containing arginine-glycine-aspartic acid (RGD), wherein the nRGD polypeptide can target tumor vessels, tumor cells and tumor-associated macrophages, and mediate the targeted delivery of tumors.

A series of cationic cyclic peptides, useful for the treatment of infectious diseases in both human and veterinary clinical/surgical environment are described herein. The peptides of the invention have a length of 15 to 21 amino acids, and show a sequence A-B-C-D-C-B-A, wherein units A and A correspond to NH.sub.2 terminal and COOH terminal regions; units B and B correspond to cyclizable amino acids containing sulfur; units C and C are sequences of 5 amino acids selected among hydrophobic amino acids, basic amino acids and amino acids forming hydrogen bonds; unit D is a dipeptide consisting of glycine and one basic amino acid. Said peptides show significant antibacterial activity, associated with high stability and resistance to the action of bacterial endopeptidases, and weak or null toxicity against eukaryotic cells.

A series of cationic cyclic peptides, useful for the treatment of infectious diseases in both human and veterinary clinical/surgical environment are described herein. The peptides of the invention have a length of 15 to 21 amino acids, and show a sequence A-B-C-D-C-B-A, wherein units A and A correspond to NH.sub.2 terminal and COOH terminal regions; units B and B correspond to cyclizable amino acids containing sulfur; units C and C are sequences of 5 amino acids selected among hydrophobic amino acids, basic amino acids and amino acids forming hydrogen bonds; unit D is a dipeptide consisting of glycine and one basic amino acid. Said peptides show significant antibacterial activity, associated with high stability and resistance to the action of bacterial endopeptidases, and weak or null toxicity against eukaryotic cells.

Disclosed is a general, reversible bicyclization strategy to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.

Disclosed is a general, reversible bicyclization strategy to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.

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 present invention provides a Plexin-binding regulating agent containing a cyclic peptide having an Arg-Trp-Thr structure or a Leu-Ser-Trp structure or a pharmaceutically acceptable salt of the cyclic peptide.

The present invention provides a Plexin-binding regulating agent containing a cyclic peptide having an Arg-Trp-Thr structure or a Leu-Ser-Trp structure or a pharmaceutically acceptable salt of the cyclic peptide.