The generation and characterisation of antagonist RNA aptamers to MCP‐1

FEBS Letters

Chapman, Trevor⁴  Parsons, Sarah³  Rhodes, Andrew¹  Rees, Stephen¹  Smithers, Nick² 

[1] Molecular Discovery Department, Glaxo Wellcome Research and Development, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK;Molecular Pharmacology Department, Glaxo Wellcome Research and Development, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK;In vitro Pharmacology Department, Glaxo Wellcome Research and Development, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK;Molecular Recognition Department, Glaxo Wellcome Research and Development, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK

关键词: Aptamer;    Monocyte chemoattractant protein-1;    Proteomics;    CCR2;    Inflammation;   

DOI  :  10.1016/S0014-5793(01)02895-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Monocyte chemoattractant protein-1 (MCP-1) has been implicated as a powerful pro-inflammatory mediator and may represent a potentially important, therapeutic opportunity for treatment of inflammatory disease and atherosclerosis. To further investigate the role of MCP-1 in inflammatory disorders we have isolated a series of RNA aptamers that bind specifically to mouse MCP-1. The highest affinity aptamers, designated ADR7 and ADR22, have been functionally characterised in vitro and in cell based assays. ADR7 and ADR22 have an affinity of 180 pM and 370 pM respectively for mouse MCP-1, they can antagonise MCP-1 binding to heparin and specifically antagonise MCP-1 induced chemotaxis in a cell based assay. An interesting feature of ADR22 but not ADR7 is that it is capable of antagonising the function of human MCP-1, demonstrating the high level of specificity of these aptamers and that the aptamers recognise MCP-1 in different ways. The aptamers may be used as a tool to further investigate the role of MCP-1 in inflammatory disorders and may also have a role as a therapeutic agent.

【 授权许可】

Unknown