Novel Cyclic Peptides and Methods Using Same

A cyclic compound of formula (I), or a salt, solvate, enantiomer or diastereoisomer thereof:

• Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-P1 (I),
• wherein in (I):
• Xaa1 is selected from the group consisting of absent, Glu and Arg;
• Xaa2 is selected from the group consisting of absent, Gly, Phe, Lys, Asp, Glu, Ile, Arg and Cit;
• Xaa3 is selected from the group consisting of absent, Asn, Asp, Ile, Glu and 2-cyclohexylglycine;
• Xaa4 is selected from the group consisting of Asn and Asp;
• Xaa5 is a modified glycine of formula (III)
• wherein in (III) R is selected from the group consisting of C1-C6 alkyl and C3-C6 cycloalkyl;
• Xaa6 is the modified proline of formula (IV)
• wherein in (IV) R is selected from the group consisting of naphthyl, p-methyl phenyl, p-ethyl phenyl, 2-phenylethyl, 1-adamantyl, 2-adamantyl and metallocene;
• Xaa7 is selected from the group consisting of Trp and 3-(3-benzothienyl)-L-alanine;
• Xaa8 is selected from the group consisting of Ser, Thr, 2,4-diaminobutanoic acid, Orn and Lys;
• Xaa9 is selected from the group consisting of absent, 2,4-diaminobutanoic acid, Orn, Lys, Glu, Glu-Ala, Glu-Ala-Met, Glu-Ala-Met-Met, and 2-(2-(2-aminoethoxy)ethoxy)acetic acid;
• P1 is absent, or is a group that comprises at least one thiol group and is covalently linked through an amide bond to (i) the C-terminus of Xaa9 if Xaa9 is not absent, or (ii) the C-terminus of Xaa8 if Xaa9 is absent;
• the side chain amino group of one residue selected from the group consisting of 2,4-diaminobutanoic acid at Xaa8, Orn at Xaa8, Lys at Xaa8, 2,4-diaminobutanoic acid at Xaa9, Orn at Xaa9, and Lys at Xaa9 forms an amide bond with the side chain carboxylic acid group of one residue selected from the group consisting of Glu at Xaa2, Asp at Xaa2, Glu at Xaa3, Asp at Xaa3 and Asp at Xaa4;
• and
• the C-terminus of Xaa8 is optionally amidated if Xaa9 and P1 are absent, or the C-terminus of Xaa9 is optionally amidated if P1 is absent.