公开(公告)号：US20120045849A1

公开(公告)日：2012-02-23

申请号：US13214355

申请日：2011-08-22

申请人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

发明人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

IPC分类号： G01N33/68 ,  G01N21/64

CPC分类号： G01N21/6486 ,  G01N1/38 ,  G01N33/6803 ,  G01N35/1065 ,  G01N35/1072

摘要： A system and method for determining the dissociation constant for a particular ligand is disclosed. In accordance with certain embodiments, the method creates a chemical denaturation curve of a protein in the absence of the ligand. A particular point is selected from this curve, such as the point at which 90% of the protein is unfolded. The molarity of chemical denaturant is determined for this selected point. A one point test is then performed for the protein with a predetermined concentration of the particular ligand. The fraction of protein which is unfolded at this point is then used to determine the dissociation constant for the ligand. This constant is used to quickly determine whether a particular ligard is well suited to be considered a potential drug candidate against that protein target.

摘要翻译： 公开了用于确定特定配体的解离常数的系统和方法。 根据某些实施方案，该方法在不存在配体的情况下产生蛋白质的化学变性曲线。 从该曲线中选择特定的点，例如90％蛋白质展开的点。 测定化学变性剂的摩尔浓度。 然后对具有预定浓度的特定配体的蛋白进行一点测试。 然后将此处展开的蛋白质的级分用于确定配体的解离常数。 该常数用于快速确定特定的基因是否非常适合被认为是针对该蛋白质靶标的潜在药物候选物。

公开(公告)号：US08609040B2

公开(公告)日：2013-12-17

申请号：US13214361

申请日：2011-08-22

申请人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

发明人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

IPC分类号： B01L3/02

CPC分类号： G01N21/6486 ,  G01N1/38 ,  G01N33/6803 ,  G01N35/1065 ,  G01N35/1072

摘要： A system for automatically creating a denaturation curve is disclosed. In accordance with certain embodiments, a movement system including a unit having a plurality of cannulas is used. The cannulas are in fluid communication with a fluid system, which allows the cannulas to draw in and dispense fluid. A measurement system is included which draws fluid from a well into a detector to determine a characteristic of the fluid. A controller is used to control these systems and also to create a denaturation graph from the measured characteristics. In another embodiment, a plurality of formulations may be created using the system.

摘要翻译： 公开了一种自动生成变性曲线的系统。 根据某些实施例，使用包括具有多个插管的单元的移动系统。 插管与流体系统流体连通，这允许插管吸入和分配流体。 包括测量系统，其将流体从井抽入检测器以确定流体的特性。 控制器用于控制这些系统，并且还可以根据测量的特征创建变性图。 在另一个实施方案中，可以使用该系统产生多种制剂。

公开(公告)号：US08859295B2

公开(公告)日：2014-10-14

申请号：US13214355

申请日：2011-08-22

申请人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

发明人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

IPC分类号： G01N33/566 ,  G01N35/10 ,  G01N33/68

CPC分类号： G01N21/6486 ,  G01N1/38 ,  G01N33/6803 ,  G01N35/1065 ,  G01N35/1072

摘要： A system and method for determining the dissociation constant for a particular ligand is disclosed. In accordance with certain embodiments, the method creates a chemical denaturation curve of a protein in the absence of the ligand. A particular point is selected from this curve, such as the point at which 90% of the protein is unfolded. The molarity of chemical denaturant is determined for this selected point. A one point test is then performed for the protein with a predetermined concentration of the particular ligand. The fraction of protein which is unfolded at this point is then used to determine the dissociation constant for the ligand. This constant is used to quickly determine whether a particular ligard is well suited to be considered a potential drug candidate against that protein target.

摘要翻译： 公开了用于确定特定配体的解离常数的系统和方法。 根据某些实施方案，该方法在不存在配体的情况下产生蛋白质的化学变性曲线。 从该曲线中选择特定的点，例如90％蛋白质展开的点。 测定化学变性剂的摩尔浓度。 然后对具有预定浓度的特定配体的蛋白进行一点测试。 然后将此处展开的蛋白质的级分用于确定配体的解离常数。 该常数用于快速确定特定的基因是否非常适合被认为是针对该蛋白质靶标的潜在药物候选物。

公开(公告)号：US20120045841A1

公开(公告)日：2012-02-23

申请号：US13214357

申请日：2011-08-22

申请人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

发明人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

IPC分类号： G01N33/68 ,  G01N21/64

CPC分类号： G01N21/6486 ,  G01N1/38 ,  G01N33/6803 ,  G01N35/1065 ,  G01N35/1072

摘要： A system and method for creating a plurality of denaturation curves is disclosed. In accordance with certain embodiments, one variable, such as salt content, pH or another parameter, is varied to create a plurality of different buffer solutions. Each is then used to create a denaturation graph. The plurality of denaturation graphs allows analysis of the effect of that variable on protein stability.

摘要翻译： 公开了一种用于产生多个变性曲线的系统和方法。 根据某些实施方案，改变一个变量，例如盐含量，pH或另一参数，以产生多个不同的缓冲溶液。 然后每个都用于创建变性图。 多个变性图可以分析该变量对蛋白质稳定性的影响。

公开(公告)号：US20120045846A1

公开(公告)日：2012-02-23

申请号：US13214353

申请日：2011-08-22

申请人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

发明人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

IPC分类号： G01N21/64 ,  C09K3/00

CPC分类号： G01N21/6486 ,  G01N1/38 ,  G01N33/6803 ,  G01N35/1065 ,  G01N35/1072

摘要： A system and method for creating a buffer solution having a desired pH value is disclosed. The method uses two known buffer solutions, each with predetermined pH values, and determines a mathematical relationship which defines the amount of each known buffer solution needed to create the buffer solution with the desired pH. This method can then be used to create one or more denaturation graphs, which demonstrate the stability of a protein at a given pH level.

摘要翻译： 公开了一种用于产生具有所需pH值的缓冲溶液的系统和方法。 该方法使用两个已知的缓冲溶液，每个具有预定的pH值，并确定数学关系，其定义了产生具有所需pH的缓冲溶液所需的每种已知缓冲溶液的量。 然后可以使用该方法来产生一个或多个变性图，其证明在给定pH水平下蛋白质的稳定性。

公开(公告)号：US20120045367A1

公开(公告)日：2012-02-23

申请号：US13214361

申请日：2011-08-22

申请人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

发明人： Richard Brown ,  Burleigh Hutchins ,  Ernesto Freire

IPC分类号： G01N33/50

CPC分类号： G01N21/6486 ,  G01N1/38 ,  G01N33/6803 ,  G01N35/1065 ,  G01N35/1072

摘要： A system for automatically creating a denaturation curve is disclosed. In accordance with certain embodiments, a movement system including a unit having a plurality of cannulas is used. The cannulas are in fluid communication with a fluid system, which allows the cannulas to draw in and dispense fluid. A measurement system is included which draws fluid from a well into a detector to determine a characteristic of the fluid. A controller is used to control these systems and also to create a denaturation graph from the measured characteristics. In another embodiment, a plurality of formulations may be created using the system.

摘要翻译： 公开了一种自动生成变性曲线的系统。 根据某些实施例，使用包括具有多个插管的单元的移动系统。 插管与流体系统流体连通，这允许插管吸入和分配流体。 包括测量系统，其将流体从井抽入检测器以确定流体的特性。 控制器用于控制这些系统，并且还可以根据测量的特征创建变性图。 在另一个实施方案中，可以使用该系统产生多种制剂。