Compstatin analogs with improved activity
View Patent ↗Compounds comprising peptides and peptidomimetics capable of binding the C3 protein and inhibiting complement activation are disclosed. These compounds display improved complement activation-inhibitory activity as compared with currently available compounds. Isolated nucleic acid molecules encoding the peptides are also disclosed.
1. An isolated nucleic acid molecule encoding one or more peptides that inhibits complement activation, wherein the peptide produced by expression of the nucleic acid molecule comprises amino acid sequence:
(SEQ ID NO: 15)
Xaa1-Cys-Val-Xaa2-Gln-Asp-Trp-Gly-Xaa3-His-Arg-
Cys-Xaa4;
wherein:
Xaa1 is Ile, Val, Leu, or a dipeptide comprising Gly-Ile;
Xaa2 is Trp;
Xaa3 is His, Ala, Phe or Trp; and
Xaa4 is L-Thr, D-Thr, Ile, Val, Gly, or a tripeptide comprising Thr-Ala-Asn;
wherein the two Cys residues are joined by a disulfide bond.
2. The isolated nucleic acid molecule of claim 1 , encoding a peptide comprising the amino acid sequence of SEQ ID NO:15, wherein Xaa3 is Ala.
3. The isolated nucleic acid molecule of claim 2 , encoding a peptide comprising the amino acid sequence of SEQ ID NO:14.
4. The isolated nucleic acid molecule of claim 3 , encoding a concatemer of two or more of a peptide comprising the amino acid sequence of SEQ ID NO:14, wherein the encoded concatemer is cleavable by hydrazine to form a multiplicity of peptides comprising SEQ ID NO:14.
5. An expression vector comprising the isolated nucleic acid molecule of claim 1 .
6. A bacterial, fungal, plant or insect cell comprising the expression vector of claim 5 .