Conformationally constrained backbone cyclized interleukin-6 antagonists
View Patent ↗Novel peptides which are conformationally constrained backbone cyclized antagonists of IL-6, are disclosed. Methods for synthesizing the IL-6 antagonists are also disclosed. Furthermore, pharmaceutical compositions comprising IL-6 antagonists, and methods of using such compositions are disclosed.
1. A backbone cyclized peptide analog having IL-6 antagonist activity, having the general formula 3:
wherein
m and n are 1 to 5;
X designates a terminal carboxy acid, amide or alcohol group;
R 1 is (D)Bip, Gln, Lys, Lys(ZCL) or Dab;
R 2 is (D)Lys, Gly, Ala or Trp
R 3 is Orn, 4PyrAla, (L) or (D)Dab, (D)Arg, Lys or Dpr;
R 4 is Lys, Lys(ZCL), Arg, Arg(Mtr) or (D)Glu;
R 5 is Asn, Trp or (D)Ala;
R 6 is Arg, (p-NO 2 )Phe, (L) or (D)Trp, Gln, Abu or Glu; and
Y 2 is amide, thioether, thioester or disulfide.
2. A pharmaceutical composition comprising a backbone cyclized IL6 antagonist wherein the IL-6 antagonist has the general formula 3:
wherein
m and n are 1 to 5;
X designates a terminal carboxy acid, amide or alcohol group;
R 1 is (D)Bip, Gln, Lys, Lys(ZCL) or Dab;
R 2 is (D)Lys, Gly, Ala or Trp
R 3 is Orn, 4PyrAla, (L) or (D)Dab, (D)Arg, Lys or Dpr;
R 4 is Lys, Lys(ZCL), Arg, Arg(Mtr) or (D)Glu;
R 5 is Asn, Trp or (D)Ala;
R 6 is Arg, (p-NO2)Phe, (L) or (D)Trp, Gln, Abu or Glu; and
Y 2 is amide, thioether, thioester or disulfide.