pH-SENSITIVE CYCLIC PEPTIDES

Abstract

The present subject matter provides pH triggered peptides, as well as compositions methods, devices, and systems comprising the same. The pH triggered peptides include cyclic and short linear peptides, and may have higher affinity to a membrane lipid bilayer at low pH than at neutral or high pH.

1 .- 95 . (canceled) 
     
     
         96 . A method for treating inflammation in a subject, the method comprising administering a composition comprising a cyclic peptide comprising at least 4 amino acids, wherein (a) at least 2 of the at least 4 amino acids of said cyclic peptide are non-polar amino acids, (b) at least 1 of the at least 4 amino acids of said cyclic peptide is a protonatable amino acid, and (c) the peptide has a higher affinity to a membrane lipid bilayer at pH 5.0 compared to at pH 8.0. 
     
     
         97 . The method of  claim 96 , wherein the cyclic peptide comprises the sequence c[E 4 W 5 C](SEQ ID NO: 5); c[E 5 K]W 5 C (SEQ ID NO: 192); c[E 5 W 5 C] (SEQ ID NO: 216); c[E 4 W 4 C] (SEQ ID NO: 217); or c[E 5 K]W 4 C (SEQ ID NO: 194). 
     
     
         98 . The method of  claim 96 , wherein the cyclic peptide comprises a functional group to which a cargo compound is attached. 
     
     
         99 . The method of  claim 98 , wherein the cargo is directly linked by a covalent bond. 
     
     
         100 . The method of  claim 98  wherein, (a) the functional group is a side chain of an amino acid of the cyclic peptide; (b) the functional group is an amino acid side chain to which a cargo compound is attached via a disulfide bond; (c) the functional group to which a cargo compound is attached comprises a free sulfhydryl (SH) or selenohydryl (SeH) group; (d) the functional group comprises a cysteine, homocysteine, selenocysteine, or homoselenocysteine; or (e) the functional group comprises a primary amine. 
     
     
         101 . The method of  claim 98 , wherein the cargo comprises a corticosteroid, an antihistamine, an immunosuppressant, or an immunomodulator. 
     
     
         102 . The method of  claim 96 , wherein the composition is administered orally, topically, intravenously, transdermally, by lavage of the area, inhalation, or injection. 
     
     
         103 . The method of  claim 96 , wherein the composition is formulated as a mouthwash. 
     
     
         104 . The method of  claim 96 , wherein the inflammation comprises arthritis, eczema, or rosacea. 
     
     
         105 . The method of  claim 96 , wherein the inflammation comprises skin damage caused after sun exposure. 
     
     
         106 . The method of  claim 96 , wherein the cyclic peptide has a net negative charge at a pH of about 7, 7.25, 7.5, or 7.75 in water. 
     
     
         107 . The method of  claim 96 , wherein the cyclic peptide has an acid dissociation constant at logarithmic scale (pKa) of less than about 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, or 7. 
     
     
         108 . The method of  claim 96 , wherein less than 1, 2, 3, 4, or 5 of the amino acids in the cyclic peptide have a net positive charge at a pH of 7, 7.25, 7.5, or 7.75 in water. 
     
     
         109 . A composition comprising a cyclic peptide comprising at least 4 amino acids, wherein (a) at least 2 of the at least 4 amino acids of said cyclic peptide are non-polar amino acids, (b) at least 1 of the at least 4 amino acids of said cyclic peptide is a protonatable amino acid, and (c) the peptide has a higher affinity to a membrane lipid bilayer at pH 5.0 compared to at pH 8.0. 
     
     
         110 . The composition of  claim 109 , wherein the cyclic peptide comprises the sequence c[E 4 W 5 C] (SEQ ID NO: 5); c[E 5 K]W 5 C (SEQ ID NO: 192); c[E 5 W 5 C] (SEQ ID NO: 216); c[E 4 W 4 C] (SEQ ID NO: 217); or c[E 5 K]W 4 C (SEQ ID NO: 194). 
     
     
         111 . The composition of  claim 109 , wherein the cyclic peptide comprises a functional group to which a cargo compound is attached. 
     
     
         112 . The composition of  claim 109 , wherein the cargo comprises a corticosteroid, an antihistamine, an immunosuppressant, or an immunomodulator. 
     
     
         113 . The composition of  claim 109 , wherein the composition further comprises a carrier in the form of an emulsion, paste, cream, lotion, gel, oil, ointment, suspension, aerosol spray, powder, aerosol powder, or semi-solid formulation