公开(公告)号：US5342585A

公开(公告)日：1994-08-30

申请号：US989764

申请日：1992-12-14

Applicant: Michal Lebl ,  Jutta Eichler ,  Vit Pokorny ,  Jiri Jehnicka ,  Petr Mudra ,  Karel Zenisek ,  Alena Stierandova ,  Jan Kalousek ,  Jan Bolf

Inventor： Michal Lebl ,  Jutta Eichler ,  Vit Pokorny ,  Jiri Jehnicka ,  Petr Mudra ,  Karel Zenisek ,  Alena Stierandova ,  Jan Kalousek ,  Jan Bolf

IPC: C07K17/04 ,  B01J19/00 ,  B01J19/22 ,  C07K1/04 ,  C07K17/08 ,  C40B40/10 ,  C40B60/14 ,  G01N21/00

CPC classification number: B01J19/22 ,  B01J19/0046 ,  C07K1/045 ,  B01J2219/00364 ,  B01J2219/00475 ,  B01J2219/00488 ,  B01J2219/00527 ,  B01J2219/00531 ,  B01J2219/00533 ,  B01J2219/00536 ,  B01J2219/00585 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00603 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00639 ,  B01J2219/00641 ,  B01J2219/00659 ,  B01J2219/00689 ,  B01J2219/00725 ,  C40B40/10 ,  C40B60/14 ,  Y10S530/811 ,  Y10S530/815

Abstract: An apparatus is disclosed for performing a multiple synthesis of peptides on a solid carrier. Active components are successively bonded to functional groups anchored on a carrier. The carrier comprises a planar porous material divided into functionalized compartments, into which an active component is put, via a dispensing head.

Abstract translation: 公开了用于在固体载体上进行多肽合成的装置。 活性组分连续键合到锚定在载体上的官能团。 载体包括通过分配头分成功能化隔室的平面多孔材料，活性组分放入其中。

公开(公告)号：US06759384B1

公开(公告)日：2004-07-06

申请号：US09211715

申请日：1998-12-14

Applicant: Fahad Al-Obeidi ,  Michal Lebl ,  James A. Ostrem ,  Pavel Safar ,  Alena Stierandova ,  Peter Strop ,  Armin Walser

Inventor： Fahad Al-Obeidi ,  Michal Lebl ,  James A. Ostrem ,  Pavel Safar ,  Alena Stierandova ,  Peter Strop ,  Armin Walser

IPC: A61K3855

CPC classification number: 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

Abstract: The invention provides compounds which specifically inhibit factor Xa activity having the structure A1—A2—(A3)m—B, where m is 0 or 1. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a Ki≦100 &mgr;M, 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.

Abstract translation: 本发明提供特异性抑制具有结构A1-A2-（A3）mB的因子Xa活性的化合物，其中m为0或1.本发明的化合物的特征在于其部分表现出对因子Xa的特异性抑制 Ki <=100μM，优选<= 2nM的活性，并且基本上不抑制参与凝血级联的其它蛋白酶的活性。 本发明还提供了特异性抑制因子Xa的活性和在体外和个体中抑制血液凝固的方法以及检测因子Xa水平或活性的方法。

公开(公告)号：US5202418A

公开(公告)日：1993-04-13

申请号：US645121

申请日：1991-01-24

Applicant: Michal Lebl ,  Jutta Eichler ,  Vit Pokorny ,  Jiri Jehnicka ,  Petr Mudra ,  Karel Zenisek ,  Alena Stierandova ,  Jan Kalousek ,  Jan Bolf

Inventor： Michal Lebl ,  Jutta Eichler ,  Vit Pokorny ,  Jiri Jehnicka ,  Petr Mudra ,  Karel Zenisek ,  Alena Stierandova ,  Jan Kalousek ,  Jan Bolf

IPC: C07K17/04 ,  B01J19/00 ,  B01J19/22 ,  C07K1/04 ,  C07K17/08 ,  C40B40/10 ,  C40B60/14

CPC classification number: B01J19/22 ,  B01J19/0046 ,  C07K1/045 ,  B01J2219/00364 ,  B01J2219/00475 ,  B01J2219/00488 ,  B01J2219/00527 ,  B01J2219/00531 ,  B01J2219/00533 ,  B01J2219/00536 ,  B01J2219/00585 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00603 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00639 ,  B01J2219/00641 ,  B01J2219/00659 ,  B01J2219/00689 ,  B01J2219/00725 ,  C40B40/10 ,  C40B60/14 ,  Y10S530/811 ,  Y10S530/815

Abstract: The invention relates to a method and apparatus for performing a multiple synthesis of peptides on a solid carrier. Active components are successively bonded to functional groups anchored on a carrier. The carrier planar functionalized porous material divided into compartments, into which the needed activated component is put. Common operations of the synthesis are carried out by all compartments of the carrier at the same time.

公开(公告)号：US5849510A

公开(公告)日：1998-12-15

申请号：US947794

申请日：1997-10-08

Applicant: Fahad Al-Obeidi ,  Michal Lebl ,  James A. Ostrem ,  Pavel Safar ,  Alena Stierandova ,  Peter Strop ,  Armin Walser

Inventor： Fahad Al-Obeidi ,  Michal Lebl ,  James A. Ostrem ,  Pavel Safar ,  Alena Stierandova ,  Peter Strop ,  Armin Walser

IPC: A61K38/00 ,  C07K5/02 ,  C07K5/06 ,  C07K5/065 ,  C07K5/068 ,  C07K5/083 ,  C07K5/087 ,  C07K5/09 ,  C07K5/097 ,  C07K5/103 ,  C07K5/107 ,  C07K7/06 ,  C07K14/81 ,  C12Q1/56 ,  C12Q1/00 ,  G01N33/53

CPC classification number: C07K7/06 ,  C07K14/811 ,  C07K5/0207 ,  C07K5/06034 ,  C07K5/06078 ,  C07K5/06086 ,  C07K5/0806 ,  C07K5/0812 ,  C07K5/0815 ,  C07K5/0821 ,  C07K5/101 ,  C07K5/1016 ,  C12Q1/56 ,  A61K38/00 ,  Y02P20/55 ,  Y10T436/105831

Abstract: The invention provides compounds which specifically inhibit factor Xa activity. The compounds consist of the structure X.sub.1 -YIR-X.sub.2, wherein X.sub.1 is H, acyl, alkyl, acylalkyl, arylalkyl or one or more amino acids, and X.sub.2 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).sub.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 K.sub.i of .ltoreq.100 .mu.M, preferably .ltoreq.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.

Abstract translation: 本发明提供特异性抑制因子Xa活性的化合物。 化合物由结构X1-YIR-X2组成，其中X1是H，酰基，烷基，酰基烷基，芳基烷基或一个或多个氨基酸，X2是修饰的C端基，一个或多个羧基保护基或一个 或更多的氨基酸或其他取代基，Y，I和R分别是酪氨酸，异亮氨酸和精氨酸，或分别具有与Y，I和R相同功能活性的拟肽或有机结构。 此外，本发明提供具有结构A1-A2-（A3）m-B的化合物，其中m为0或1.本发明的化合物可以是直链或环状的，并且其长度可以为约2和43个残基。 本发明的化合物的特征在于其部分表现出具有Ki =100μM，优选

公开(公告)号：US5338831A

公开(公告)日：1994-08-16

申请号：US992288

申请日：1992-12-14

Applicant: Michal Lebl ,  Jutta Eichler ,  Vit Pokorny ,  Jifi Jehnicka ,  Petr Mudra ,  Karel Zenisek ,  Alena Stierandova ,  Jan Kalousek ,  Jan Bolf

Inventor： Michal Lebl ,  Jutta Eichler ,  Vit Pokorny ,  Jifi Jehnicka ,  Petr Mudra ,  Karel Zenisek ,  Alena Stierandova ,  Jan Kalousek ,  Jan Bolf

IPC: C07K17/04 ,  B01J19/00 ,  B01J19/22 ,  C07K1/04 ,  C07K17/08 ,  C40B40/10 ,  C40B60/14 ,  A61K37/02

CPC classification number: B01J19/22 ,  B01J19/0046 ,  C07K1/045 ,  B01J2219/00364 ,  B01J2219/00475 ,  B01J2219/00488 ,  B01J2219/00527 ,  B01J2219/00531 ,  B01J2219/00533 ,  B01J2219/00536 ,  B01J2219/00585 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00603 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00639 ,  B01J2219/00641 ,  B01J2219/00659 ,  B01J2219/00689 ,  B01J2219/00725 ,  C40B40/10 ,  C40B60/14 ,  Y10S530/811 ,  Y10S530/815

Abstract: A method is disclosed for performing a multiple synthesis of peptides on a solid carrier. Active components are successively bonded to functional groups anchored on a carrier. The carrier is a planar porous material divided into functionalized compartments, into which an active component is put, via a dispensing head.

Abstract translation: 公开了一种在固体载体上进行多肽合成的方法。 活性组分连续键合到锚定在载体上的官能团。 载体是通过分配头分成功能化隔室的平面多孔材料，活性成分被放入其中。