GENE REGULATION

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 X₂X₃ W X₄ X₅ X₆X₇X₈ 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.