| 摘要 |
The invention provides a method for selecting a candidate drug compound, said method comprising i) identifying a starting oligopeptide having a binding affinity for a cell surface or other receptor site; ii) generating a plurality of homologous oligopeptides having single site amino acid modifications relative to said starting oligopeptide; iii) identifying components of said starting oligopeptide responsible for the secondary structure thereof; iv) for modification sites identified in step (ii) selecting a set of amino acids; v) for components identified in step (iii) selecting at least one non-natural amino acid which mimics the secondary structure of the component; vi) generating a first combinatorial library of oligopeptides having at said identified modification sites amino acid residues corresponding to said selected sets of amino acids; vii) identifying members of said first library having a binding affinity value above a predetermined minimum and generating a further combinatorial library of oligopeotides having members not present in said first library, and identifying members of said further library having improved binding affinity values relative to the identified members of said first library, and with the proviso that at least one of said first and further libraries contains oligopeptides containing residues of said non-natural amino acid or acids; and (viii) selecting from the identified members of said library or library a drug candidate. |
