Abstract: Compstatin analogues having improved binding and complement-inhibiting activity as compared to the 13 amino acid compstatin peptide (ICVVQDWGHHRCT (cyclic C2-C12)) are described, in particular compstatin analogues that additionally possess useful physicochemical properties, such as increased solubility. These analogues include variants with an isoleucine residue at position 3 in place of the wild type valine residue, which provides compstatin peptides with improved binding and complement-inhibiting activity and also enables the introduction of other modifications, for example modifications that are capable of increasing solubility, such as the introduction of charged or polar amino acids at position 9 and/or the introduction of N- and/or C-terminal sequences.

Abstract: Compstatin analogues having improved binding and complement-inhibiting activity as compared to the 13 amino acid compstatin peptide (ICWQDWGHHRCT (cyclic C2-C12)) are described, in particular compstatin analogues that additionally possess useful physicochemical properties. The analogues have a thioether bond rather than a disulfide bond between the side chains of the f residues corresponding to cysteines 2 and 12 of compstatin which may increase stability. The analogues may also have an isoleucine residue at position 3 in place of the wild type valine residue, which provides compstatin peptides with improved binding and complement-inhibiting activity and also enables the introduction of other modifications, for example modifications that are capable of increasing solubility, such as the introduction of charged or polar amino acids at position 9 and/or the introduction of N- and/or C-terminal sequences.