Publications [#99855] of Bruce A Sullenger

Papers Published

1. ML Jeter, LV Ly, YM Fortenberry, HC Whinna, RR White, CP Rusconi, BA Sullenger, FC Church, RNA aptamer to thrombin binds anion-binding exosite-2 and alters protease inhibition by heparin-binding serpins., FEBS letters, vol. 568 no. 1-3 (June, 2004), pp. 10-4, ISSN 0014-5793 [doi]
   (last updated on 2010/07/15)

   Abstract:
   We studied the RNA aptamer Toggle-25/thrombin interaction during inhibition by antithrombin (AT), heparin cofactor II (HCII) and protein C inhibitor (PCI). Thrombin inhibition was reduced 3-fold by Toggle-25 for AT and HCII, but it was slightly enhanced for PCI. In the presence of glycosaminoglycans, AT and PCI had significantly reduced thrombin inhibition with Toggle-25, but it was only reduced 3-fold for HCII. This suggested that the primary effect of aptamer binding was through the heparin-binding site of thrombin, anion-binding exosite-2 (exosite-2). We localized the Toggle-25 binding site to Arg 98, Glu 169, Lys 174, Asp 175, Arg 245, and Lys 248 of exosite-2. We conclude that a RNA aptamer to thrombin exosite-2 might provide an effective clinical reagent to control heparin's anticoagulant action.

   Keywords:
   Anions • Antithrombins • Base Sequence • Binding Sites • Glycosaminoglycans • Heparin • Heparin Cofactor II • Humans • Models, Molecular • Protein C Inhibitor • RNA • Thrombin • chemistry • metabolism • metabolism*