公开(公告)号：US20100216113A1

公开(公告)日：2010-08-26

申请号：US12451394

申请日：2008-05-07

申请人： Andreas Kohl ,  Said Eshaghi ,  Daniel Martinez Molina ,  Par Nordlund ,  Anders Wetterholm ,  Jesper Z. Haeggstrom

发明人： Andreas Kohl ,  Said Eshaghi ,  Daniel Martinez Molina ,  Par Nordlund ,  Anders Wetterholm ,  Jesper Z. Haeggstrom

IPC分类号： C12Q1/00 ,  G06G7/48 ,  C12N9/00

CPC分类号： C12Q1/25 ,  C07K2299/00 ,  C12N9/1085 ,  C12Y404/0102 ,  G01N33/92 ,  G01N2500/04 ,  G16B15/00

摘要： A method for selecting or designing a compound expected to modulate the activity of Leukotriene C4 synthase (LTC4S), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the catalytic site or a substrate binding region of LTC4S, wherein a three-dimensional structure of at least a part of the catalytic site or a substrate binding region of LTC4S is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said catalytic site or substrate binding region is selected. The selected compound may be predicted to bind to at least a part of a region of the structure termed the “GSH substrate binding cavity” (formed by residues including residues Arg51, Arg30, Arg104, Gln53, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Ile27, Pro37, Leu108 of full length human LTC4S, or equivalent residues); the “lipophilic substrate binding crevice” (formed by residues including Ala20, Leu24, Ile27, Tyr59, Trp116, Ala112, Leu115, Leu108, Tyr109, Leu62, Val119, Thr66, Vall6 and Leu17, or equivalent residues); or the “catalytic site” (formed by residues including Arg104 or Arg31, or equivalent residues).

摘要翻译： 选择或设计预期调节白三烯C4合酶（LTC4S）的活性的化合物的方法，所述方法包括使用分子建模手段来选择或设计预测与催化位点相互作用的化合物或底物结合 LTC4S的区域，其中将LTC4S的至少一部分催化位点或底物结合区域的三维结构与化合物的三维结构进行比较，以及预测与所述催化剂相互作用的化合物 选择位点或底物结合区。 可以预期所选择的化合物可结合称为“GSH底物结合腔”的结构的至少一部分（由残基Arg51，Arg30，Arg104，Gln53，Asn55，Glu58，Tyr59，Tyr93，Tyr97 ，全长人LTC4S的Ile27，Pro37，Leu108或相当的残基）; （由Ala20，Leu24，Ile27，Tyr59，Trp116，Ala112，Leu115，Leu108，Tyr109，Leu62，Val119，Thr66，Vall6和Leu17等残基组成的“亲脂性底物结合缝隙”）。 或“催化位点”（由包含Arg104或Arg31的残基或等同残基形成）。