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    Peptide inhibitors of inflammation mediated by selectins
    1.
    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。

    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：US06528487B1

    公开(公告)日：2003-03-04

    申请号：US08135319

    申请日：1993-10-12

    申请人： George A. Heavner ,  Rodger P. McEver ,  Jian-Guo Geng

    发明人： George A. Heavner ,  Rodger P. McEver ,  Jian-Guo Geng

    IPC分类号： A61K3808

    CPC分类号： C07K14/70564

    摘要： Peptides derived from three regions of the lectin domain of GMP-140 and the related selectins, ELAM-1 and the lymphocyte homing receptor, have seen found to inhibit neutrophil adhesion to GMP-140. These and additional peptides have been synthesized, having as their core region portions of the 56-60 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 5 to 1500 &mgr;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： 从GMP-140的凝集素结构域和相关选择素，ELAM-1和淋巴细胞归巢受体的三个区域衍生的肽已经发现抑制嗜中性粒细胞粘附到GMP-140。 已经合成了这些和额外的肽，其具有作为GMP-140的56-60氨基酸序列的核心区域部分，残基1在信号肽切割后定义为成熟蛋白的N末端。 实施例证明了嗜中性粒细胞与浓度范围为5-1500μmolol的肽的GMP-140的结合的抑制。 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。