Cyclic Natriuretic Peptide Constructs

A cyclic peptide construct with an N-terminus and a C-terminus comprising from eleven to thirteen amino acid residues with an amino acid surrogate at the C-terminus position of the following formula:

• wherein
• Y is CH2 or C═O;
• W is CH2, NH or NR″;
• Z is H or CH3;
• J is —H, —OH, —C(═O)—OH, —C(═O)—NH2, or a C-terminus capping group;
• one of Ra and Rb is H and the other of Ra and Rb is —(CH2)y—R″;
• R″ is:
• —NH2,
• —NH—C(═NH)—NH2,
• —NH—(CH2)y—NH2,
• —NH—C(═O)—NH2,
• —C(═O)—NH2,
• —C(═O)—NH—CH3,
• —C(═O)—NH—(CH2)y—NH2,
• —NH—C(═NH)—NH-Me,
• —NH—C(═NH)—NH-Et,
• —NH—C(═NH)—NH—Pr,
• —NH—C(═NH)—NH—Pr-i,
• —NH—C(═O)—CH3,
• —NH—C(═O)—CH2—CH3,
• —NH—C(═O)—CH—(CH3)2,
• —NH—C(═O)—O—CH3,
• —NH—C(═O)—O—CH2—CH3,
• —NH—C(═O)—O—C—(CH3)3,
• —NH—C(═O)—NH—CH3,
• —NH—C(═N—C(═O)—O—C—(CH3)3)—NH—C(═O)—O—C—(CH3)3,
• —N(C(═O)—O—C—(CH3)3)—C(═NH)—NH—C(═O)—O—C—(CH3)3,
• R′″ is an acyl, a C1 to C17 linear or branched alkyl chain, a C2 to C19 linear or branched alkyl acyl chain, a Ci to C17 linear or branched omega amino aliphatic, or a Ci to C17 linear or branched omega amino aliphatic acyl;
• x is 1 or 2;
• y is 1 to 5;
• n is 0, 1 or 2;
• and
• the carbon atoms marked with an asterisk can have any stereochemical configuration;
• with the amino acid surrogate at the C-terminus position being covalently bonded to the immediately adjacent amino acid residue.