公开(公告)号：EP0705279B1

公开(公告)日：2003-02-19

申请号：EP94919294.2

申请日：1994-05-27

申请人： SELECTIDE CORPORATION

发明人： LEBL, Michal ,  LAM, Kit S. ,  SALMON, Sydney E. ,  KRCHNAK, Victor ,  SEPETOV, Nikolai ,  KOCIS, Peter

IPC分类号： C07K17/00 ,  C12Q1/68 ,  C12P21/00

CPC分类号： C07K1/047 ,  B01J2219/00572 ,  B01J2219/00596 ,  C40B70/00

摘要： The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports. In particular, the invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. Each of the solid phase synthesis support beads contains a single type of synthetic test compound. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon-carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided. The invention also relates to methods of synthesizing such libraries and the use of such libraries to identify and characterize molecules of interest from among the library of synthetic test compound.

公开(公告)号：EP0705279A1

公开(公告)日：1996-04-10

申请号：EP94919294.0

申请日：1994-05-27

申请人： SELECTIDE CORPORATION

发明人： LEBL, Michal ,  LAM, Kit S. ,  SALMON, Sydney E. ,  KRCHNAK, Victor ,  SEPETOV, Nikolai ,  KOCIS, Peter

IPC分类号： G01N33 ,  C07B61 ,  C07K1 ,  C07K17 ,  C40B70

CPC分类号： C07K1/047 ,  B01J2219/00572 ,  B01J2219/00596 ,  C40B70/00

摘要： The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports. In particular, the invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. Each of the solid phase synthesis support beads contains a single type of synthetic test compound. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon-carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided. The synthetic test compound can also be molecular scaffolds, such as derivatives of monocyclic of bicyclic carbohydrates, steroids, sugars, heterocyclic structures, polyaromatic structures, or other structures capable of acting as a scaffolding. Examples of suitable molecular scaffolds are provided. The invention also relates to methods of synthesizing such libraries and the use of such libraries to identify and characterize molecules of interest from among the library of synthetic test compound.

公开(公告)号：EP0797776A1

公开(公告)日：1997-10-01

申请号：EP95942579.0

申请日：1995-12-07

申请人： SELECTIDE CORPORATION

发明人： LEBL, Michal

IPC分类号： B01J19 ,  C07B61 ,  C07K1 ,  C40B30 ,  G01N33 ,  C40B40 ,  C40B60 ,  C40B70

CPC分类号： C40B30/04 ,  B01J19/0046 ,  B01J2219/00315 ,  B01J2219/00515 ,  B01J2219/00527 ,  B01J2219/00545 ,  B01J2219/00554 ,  B01J2219/0059 ,  B01J2219/00592 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00637 ,  B01J2219/00644 ,  B01J2219/00657 ,  B01J2219/00659 ,  B01J2219/00725 ,  C07B2200/11 ,  C07K1/047 ,  C40B40/10 ,  C40B60/14 ,  C40B70/00 ,  G01N33/54353 ,  G01N33/6845

摘要： A technique is disclosed for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

公开(公告)号：EP0751779B1

公开(公告)日：2001-12-19

申请号：EP94920294.9

申请日：1994-06-21

申请人： SELECTIDE CORPORATION

发明人： LEBL, Michal ,  KRCHNAK, Viktor ,  KOCIS, Petr ,  LAM, Kit S.

IPC分类号： A61K38/00

CPC分类号： C07K1/042

摘要： The present invention is directed to linkers based on ester bond linkages, especially iminodiacetic acid ester bond linkages, for use in solid phase peptide synthesis. In particular, the invention is directed to cleavable linkers that can release peptide from the solid phase support under relatively mild conditions by formation of a diketopiperazine or other cyclic structure, such that the cyclic structure remains on the solid phase support, and, in a second cleavage, under more stringent conditions of high pH. The invention is further directed to solid phase supports prepared with multiple cleavable linkers, including a linker that is cleaved by formation of a cyclic product. One such second linker is an ester of hydroxymethylbenzoic acid, or esters formed by carboxy groups of aspartic or glutamic acid.

公开(公告)号：EP0804281A1

公开(公告)日：1997-11-05

申请号：EP96906212.0

申请日：1996-01-19

申请人： SELECTIDE CORPORATION

发明人： KRCHNAK, Viktor ,  LEBL, Michal ,  SELIGMANN, Bruce

IPC分类号： B01J19 ,  B25J9 ,  C07K1 ,  C40B40 ,  C40B60

CPC分类号： B25J9/1679 ,  B01J19/0046 ,  B01J2219/00288 ,  B01J2219/0029 ,  B01J2219/00308 ,  B01J2219/00351 ,  B01J2219/00353 ,  B01J2219/00416 ,  B01J2219/00418 ,  B01J2219/00423 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00689 ,  B01J2219/00691 ,  B01J2219/00695 ,  B01J2219/0072 ,  B01J2219/00725 ,  C07K1/045 ,  C07K1/047 ,  C40B40/10 ,  C40B60/14 ,  G05B2219/40101 ,  G05B2219/45092 ,  Y10S706/906

摘要： A solid phase synthesis system is provided by employing a fully automated robot (20) that operates with a novel timing protocol executed by a computer (25) for handling multiple synthetic tasks efficiently. The fully automated robot (20) moves along a track (35) and is equipped with a gripper arm (30) which can pick up, position, and operate syringes (40, 60) which can contain solid supports and amino acid reactants. The novel timing protocol is realized by performing steps in the synthesis cycles for different compounds, such as peptides, concurrently rather than on a sequential basis.

公开(公告)号：EP0758341A1

公开(公告)日：1997-02-19

申请号：EP95917736.0

申请日：1995-04-25

申请人： SELECTIDE CORPORATION

发明人： AL-OBEIDI, Fahad ,  LEBL, Michal ,  OSTREM, James, A. ,  SAFAR, Pavel ,  STIERANDOVA, Alena ,  STROP, Peter ,  WALSER, Armin

IPC分类号： A61K38 ,  A61P7 ,  C07K5 ,  C07K7 ,  C07K14 ,  C12Q1

CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K5/0207 ,  C07K5/06034 ,  C07K5/06078 ,  C07K5/06086 ,  C07K5/0806 ,  C07K5/0812 ,  C07K5/0815 ,  C07K5/0821 ,  C07K5/101 ,  C07K5/1016 ,  C07K7/64 ,  C07K14/811 ,  C12Q1/56 ,  Y02P20/55

摘要： The invention provides compounds which specifically inhibit factor Xa activity. The compounds consist of the structure X1-YIR-X2, wherein X1 is H, acyl, alkyl, acylalkyl, arylalkyl or one or more amino acids, and X2 is a modified C-terminal group, one or more carboxy-protecting groups or one or more amino acids or other substituent, and Y, I and R are tyrosine, isoleucine and arginine, respectively, or peptidomimetic or organic structures that possess the same functional activity as Y, I and R, respectively. In addition, the present invention provides a compound having the structure A1-A2-(A3)m-B, where m is 0 or 1. A compound of the invention can be linear or cyclic and can be about 2 and 43 residues in length. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a Ki of « 100 νM, preferably « 2 nM, and does not substantially inhibit the activity of other proteases involved in the coagulation cascade. The invention further provides methods of specifically inhibiting the activity of factor Xa and of inhibiting blood clotting in vitro and in an individual and methods of detecting factor Xa levels or activity.

公开(公告)号：EP0797776B1

公开(公告)日：2002-06-12

申请号：EP95942579.4

申请日：1995-12-07

申请人： SELECTIDE CORPORATION

发明人： LEBL, Michal

IPC分类号： C07K1/04 ,  G01N33/543

CPC分类号： C40B30/04 ,  B01J19/0046 ,  B01J2219/00315 ,  B01J2219/00515 ,  B01J2219/00527 ,  B01J2219/00545 ,  B01J2219/00554 ,  B01J2219/0059 ,  B01J2219/00592 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00637 ,  B01J2219/00644 ,  B01J2219/00657 ,  B01J2219/00659 ,  B01J2219/00725 ,  C07B2200/11 ,  C07K1/047 ,  C40B40/10 ,  C40B60/14 ,  C40B70/00 ,  G01N33/54353 ,  G01N33/6845

摘要： A technique is disclosed for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

公开(公告)号：EP0804281B1

公开(公告)日：2002-06-05

申请号：EP96906212.4

申请日：1996-01-19

申请人： SELECTIDE CORPORATION

发明人： KRCHNAK, Viktor ,  LEBL, Michal ,  SELIGMANN, Bruce

IPC分类号： C07K1/04 ,  G05B13/00 ,  B01J19/00 ,  B25J9/16

CPC分类号： B25J9/1679 ,  B01J19/0046 ,  B01J2219/00288 ,  B01J2219/0029 ,  B01J2219/00308 ,  B01J2219/00351 ,  B01J2219/00353 ,  B01J2219/00416 ,  B01J2219/00418 ,  B01J2219/00423 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00689 ,  B01J2219/00691 ,  B01J2219/00695 ,  B01J2219/0072 ,  B01J2219/00725 ,  C07K1/045 ,  C07K1/047 ,  C40B40/10 ,  C40B60/14 ,  G05B2219/40101 ,  G05B2219/45092 ,  Y10S706/906

摘要： A solid phase synthesis system is provided by employing a fully automated robot (20) that operates with a novel timing protocol executed by a computer (25) for handling multiple synthetic tasks efficiently. The fully automated robot (20) moves along a track (35) and is equipped with a gripper arm (30) which can pick up, position, and operate syringes (40, 60) which can contain solid supports and amino acid reactants. The novel timing protocol is realized by performing steps in the synthesis cycles for different compounds, such as peptides, concurrently rather than on a sequential basis.

公开(公告)号：EP0751779A1

公开(公告)日：1997-01-08

申请号：EP94920294.0

申请日：1994-06-21

申请人： SELECTIDE CORPORATION

发明人： LEBL, Michal ,  KRCHNAK, Viktor ,  KOCIS, Petr ,  LAM, Kit S.

IPC分类号： A61K38 ,  C07K5 ,  C07K1

CPC分类号： C07K1/042

摘要： The present invention is directed to linkers based on ester bond linkages, especially iminodiacetic acid ester bond linkages, for use in solid phase peptide synthesis. In particular, the invention is directed to cleavable linkers that can release peptide from the solid phase support under relatively mild conditions by formation of a diketopiperazine or other cyclic structure, such that the cyclic structure remains on the solid phase support, and, in a second cleavage, under more stringent conditions of high pH. The invention is further directed to solid phase supports prepared with multiple cleavable linkers, including a linker that is cleaved by formation of a cyclic product. One such second linker is an ester of hydroxymethylbenzoic acid, or esters formed by carboxy groups of aspartic or glutamic acid.