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    Peptide inhibitors of selectin binding
    1.
    发明授权
    Peptide inhibitors of selectin binding 失效
    选择蛋白结合肽抑制剂

    公开(公告)号：US5618785A

    公开(公告)日：1997-04-08

    申请号：US457804

    申请日：1995-06-01

    申请人： George A. Heavner ,  Marian Kruszynski ,  Miljenko Mervic

    发明人： George A. Heavner ,  Marian Kruszynski ,  Miljenko Mervic

    IPC分类号： A61K38/00 ,  C07K14/705 ,  A61K38/08 ,  C07K7/06

    CPC分类号： C07K14/70564 ,  A61K38/00

    摘要： The present invention provides novel peptides constructed to mimic the topology of the surface exposed segements of the 23-30 sequence and Tyr.sup.118 in the lectin domain of P-selectin. The invention also provides pharmaceutical compositions comprising the peptides of the invention, and diagnostic and therapeutic methods utilizing the peptides and pharmaceutical compositions of the invention.

    摘要翻译： 本发明提供了新型肽，其构建为模拟P型选择蛋白凝集素结构域中23-30序列和Tyr118的表面暴露部位的拓扑结构。 本发明还提供了包含本发明的肽的药物组合物，以及利用本发明的肽和药物组合物的诊断和治疗方法。

    Peptide inhibitors of inflammation mediated by selectins
    2.
    发明授权
    Peptide inhibitors of inflammation mediated by selectins 失效
    由选择素介导的炎症肽抑制剂

    公开(公告)号：US6111065A

    公开(公告)日：2000-08-29

    申请号：US233221

    申请日：1994-04-26

    申请人： George A. Heavner ,  Rodger P. McEver ,  Jian-Guo Geng ,  Douglas J. Riexinger ,  Marian Kruszynski ,  Leon A. Epps ,  Miljenko Mervic

    发明人： George A. Heavner ,  Rodger P. McEver ,  Jian-Guo Geng ,  Douglas J. Riexinger ,  Marian Kruszynski ,  Leon A. Epps ,  Miljenko Mervic

    IPC分类号： C07K7/06 ,  A61K38/00 ,  C07K7/08 ,  C07K14/645 ,  C07K14/705 ,  C07K14/00 ,  C07K7/04

    CPC分类号： C07K14/70564 ,  A61K38/00

    摘要： Peptides derived from three regions of the lectin domain of GMP-140 (P-selectin) and the related selectins, ELAM-1 (E-selectin) and the lymphocyte homing receptor (L-selectin), have been found to inhibit neutrophil adhesion to GMP-140. These and additional peptides have been synthesized, having as their core region portions of the 74-76 amino acid sequence of GMP-140, with residue 1 defined as the N-terminus of the mature protein after the cleavage of the signal peptide. Examples demonstrate the inhibition of the binding of neutrophils to GMP-140 of peptides in concentrations ranging from 30 to 1500 .mu.mol. It has been found that alterations within the core sequence, as well as N-terminal and C-terminal flanking regions, do not result in loss of biological activity. The peptides are useful as diagnostics and, in combination with a suitable pharmaceutical carrier, for clinical applications in the modulation or inhibition of coagulation processes or inflammatory processes.

    摘要翻译： 已经发现衍生自GMP-140（P-选择素）的凝集素结构域和相关选择素，ELAM-1（E-选择蛋白）和淋巴细胞归巢受体（L-选择蛋白））的三个区域的肽抑制嗜中性粒细胞粘附 GMP-140。 已经合成了这些和额外的肽，其具有作为其核心区域的GMP-140的74-76氨基酸序列的部分，残基1在信号肽切割后定义为成熟蛋白的N末端。 实施例证明嗜中性粒细胞与浓度范围为30至1500μmol的肽的GMP-140结合的抑制。 已经发现，核心序列以及N-末端和C-末端侧翼区中的改变不会导致生物活性的丧失。 肽可用作诊断，并且与合适的药物载体组合用于调节或抑制凝血过程或炎症过程中的临床应用。