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CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES

机译:促凋亡BAX和BCL-2多肽的化学调节剂

摘要

The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an α1 helix, α2 helix, a loop between α1-α2, α6 helix, and select residues of α4, α5, and α8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.
机译:本发明提供了鉴定调节BCL-2家族多肽活性的化合物的方法,该方法包括:a)在适合于调节所述BCL-2活性的条件下使所述BCL-2家族多肽与化合物接触。家族多肽b)检测所述化合物对所述BCL-2家族多肽的活性的调节,其中所述化合物与包含α1螺旋,α2螺旋,α1-α2,α6螺旋之间的环和一个或多个的结合位点相互作用。选择所述BCL-2家族多肽中α4,α5和α8螺旋的残基;其中化合物与结合位点的相互作用发生在具有或不具有带电和亲水性残基的周边的水平疏水槽,上六面环,下六面环或其组合。

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