| 摘要 |
The present invention relates to peptides, which impair PBX-dependent regulation of gene transcription and thus have utility in the treatment or prevention of disorders in which aberrant cell division occurs. In particular, the invention provides peptides comprising the amino acid sequence (I), Y1 X1 X2 X3 W X4 X5 X6 X7 X8 Y2 (I) wherein the sequence X1 to X8 is an amino acid sequence comprising at least 8 amino acids, which may optionally be interrupted by one or two amino acid residues between one or more of the 9 amino acid positions defined herein; X1 is selected from W, T, PE, KQI, VV, PQT, H, RI and absent; X2 is an amino acid with an aromatic side chain or cysteine; X3 is P or D; X4 is a hydrophobic amino acid X5 is an amino acid with a charged side chain; X6 is an amino acid with a basic side chain; X7 is a polar hydrophilic amino acid; X8 is one or more amino acids or absent; and Y1 and Y2 are each either absent or a peptide comprising a cationic polymer of basic amino acids, such that at least one Of Y1 and Y2 is present; and peptides comprising the amino acid sequence (II): Y3 X1 X2 X3 W X4 X5 X6 X7 X8 Y4 (II) wherein The sequence X1 to X8 is an amino acid sequence comprising at least 8 amino acids, which may optionally be interrupted by one or two amino acid residues between one or more of the 9 amino acid positions defined herein; X1 is selected from W, T, PE, KQI, VV, PQT, H, RI and absent; X2 is an amino acid with an aromatic side chain; X3 is P or D; X4 is a hydrophobic amino acid X5 is an amino acid with a charged side chain; X6 is an amino acid with a basic side chain; X7 is a polar hydrophilic amino acid; X8 is one or more amino acids or absent; and Y3 and Y4 are each either absent or a peptide comprising a sequence comprising a cell penetration moiety, such that at least one of Y3 and Y4 is present; wherein at least the N-terminal and C-terminal amino acids of said peptide is in the D-conformation.
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