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    • 8. 发明授权
    • Method for identifying active domains and amino acid residues in
polypeptides and hormone variants
    • 用于鉴定多肽和激素变体中活性结构域和氨基酸残基的方法
    • US06013478A
    • 2000-01-11
    • US104036
    • 1998-06-24
    • James A. WellsBrian C. Cunningham
    • James A. WellsBrian C. Cunningham
    • A61K38/24C07K1/00C07K14/575C07K14/61C07K16/00C12N1/21C12N15/00C12N15/16C12N15/18C12N15/63C12P21/06C12Q1/68G01N33/48G01N33/50G01N33/53G01N33/566G06F19/00
    • C07K14/575C12N15/1058Y10S530/806Y10S530/808
    • The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide. The method comprises substituting a scanning amino acid for one of the amino acid residues within the active domain of the parent polypeptide and assaying the residue-substituted polypeptide so formed with a target substance. The invention further provides polypeptide variants comprising segment-substituted and residue-substituted growth hormones, prolactins and placental lactogens.
    • 本发明提供了通过鉴定影响多肽与靶物质的活性的活性结构域来系统分析多肽的结构和功能的方法。 通过用类似物与多肽的类似多肽片段取代多肽的选定氨基酸片段来确定此类活性结构域。 与亲本多肽相比,类似物与目标物质具有不同的活性。 将段取代的多肽的活性与目标的亲本多肽的相同活性进行比较。 这些活性的比较提供了活性结构域在亲本多肽中的位置的指示。 本发明还提供鉴定亲本多肽活性结构域内活性氨基酸残基的方法。 该方法包括用扫描氨基酸取代母体多肽的活性结构域内的氨基酸残基之一,并测定与靶物质形成的残基取代的多肽。 本发明还提供了包含片段取代的和残基取代的生长激素,催乳素和胎盘乳糖的多肽变体。