公开(公告)号：WO02059272A3

公开(公告)日：2003-02-20

申请号：PCT/US0202199

申请日：2002-01-24

Applicant: UNIV COLUMBIA ,  CORNISH VIRGINIA W

Inventor： CORNISH VIRGINIA W

IPC: C07D501/00 ,  C12N15/10 ,  C12N15/62 ,  C12Q1/68 ,  A61K39/395 ,  C07K16/00

CPC classification number: C12N15/62 ,  A61K47/55 ,  C07D501/00 ,  C07K2319/00 ,  C07K2319/23 ,  C07K2319/71 ,  C07K2319/80 ,  C12N15/1055

Abstract: Described are compounds having the formula: H1-Y-H2 where H1 is a substrate capable of selectively binding to a first receptor; where H2 is a substrate capable of selectively binding to and selectively forming a covalent bond with a second receptor; and wherein Y is a molety providing a covalent linkage between H1 and H2, which may be present or absent, and when absent, H1 is covalently linked to H2. Also described are uses of the compounds for in vivo screening of compounds are proteins.

Abstract translation: 描述了具有下式的化合物：H1-Y-H2，其中H1是能够选择性结合第一受体的底物; 其中H 2是能够选择性地结合并选择性地与第二受体形成共价键的底物; 并且其中Y是提供H1和H2之间可能存在或不存在的共价键的摩尔数，当不存在时，H1与H 2共价连接。 还描述了化合物用于体内筛选化合物的用途是蛋白质。

公开(公告)号：WO2004042345A3

公开(公告)日：2004-09-23

申请号：PCT/US0312612

申请日：2003-04-24

Applicant: UNIV COLUMBIA ,  ALTHOFF ERIC A ,  CORNISH VIRGINIA W

Inventor： ALTHOFF ERIC A ,  CORNISH VIRGINIA W

IPC: C07K14/47 ,  C07K14/705 ,  C12N1/20

CPC classification number: C07K14/705 ,  C07K14/47 ,  C07K14/4705 ,  C07K2319/00

Abstract: A transgenic bacterial cell comprising (a) a dimeric small molecule which comprises a first moiety known to bind a first receptor domain covalently linked to a second moiety known to bind a second receptor domain; (b) nucleotide sequences which upon transcription encode i) a first fusion protein comprising the first receptor domain, and ii) a second fusion protein comprising the second receptor domain; and (c) a reporter gene wherein expression of the reporter gene is conditioned on the proximity of the first fusion protein to the second fusion protein. The cell is also adapted for use in a method for identifying a molecule that binds to a known target in a bacterial cell from a pool of candidate molecules, and a method for identifying an unknown target receptor to which a molecule is capable of binding in a bacterial cell. Also described are compounds and kits for carrying out the methods.

Abstract translation: 一种转基因细菌细胞，其包含（a）二聚小分子，其包含已知结合与已知结合第二受体结构域的第二部分共价连接的第一受体结构域的第一部分; （b）转录后编码的核苷酸序列，i）包含第一受体结构域的第一融合蛋白，和ii）包含第二受体结构域的第二融合蛋白; 和（c）报道基因，其中报道基因的表达以第一融合蛋白与第二融合蛋白的接近程度为条件。 该细胞还适用于鉴定与候选分子库中细菌细胞中已知靶标结合的分子的方法，以及用于鉴定分子能够在其中结合的未知靶标受体的方法 细菌细胞。 还描述了用于实施所述方法的化合物和试剂盒。

公开(公告)号：WO2008005529A3

公开(公告)日：2008-09-18

申请号：PCT/US2007015568

申请日：2007-07-05

Applicant: TRUSTEES COLUMBIA UNIVERSITY I ,  CORNISH VIRGINIA W ,  PERALTA-YAHYA PAMELA ,  BRONSON JONATHAN

Inventor： CORNISH VIRGINIA W ,  PERALTA-YAHYA PAMELA ,  BRONSON JONATHAN

IPC: C40B40/08

CPC classification number: C12N15/1058 ,  C12N15/1055 ,  C12N15/1086

Abstract: The present invention relates to systems which harness the molecular biology of a living cell to direct evolution of biological entities of interest. According to the invention, a host cell is engineered to facilitate mutation of a nucleic acid target corresponding to that entity and select for desirable mutants. As applied to populations of host cells, the invention provides a means to generate and contemporaneously select mutants of interest, allowing for the production of extremely diverse libraries enriched in the most "fit" mutants.

Abstract translation: 本发明涉及利用活细胞的分子生物学来指导目的生物实体的进化的系统。 根据本发明，将宿主细胞工程化以促进对应于该实体的核酸靶标的突变并选择期望的突变体。 当应用于宿主细胞群体时，本发明提供了产生和同时选择感兴趣突变体的手段，允许产生富含最“适合”突变体的极其不同的文库。