Abstract:
:Aptamers recognize their targets with extraordinary affinity and specificity. The aptamer-based therapeutic, Macugen, is derived from a modified 2'fluoro pyrimidine RNA inhibitor to vascular endothelial growth factor (VEGF) and is now being used to treat the wet form of age-related macular degeneration. This VEGF(165) aptamer binds specifically to the VEGF(165) isoform, a dimeric protein with a receptor-binding domain and a heparin-binding domain (HBD). To understand the molecular recognition between VEGF and this aptamer, binding experiments were used to show that the HBD contributes the majority of binding energy in the VEGF(165)-aptamer complex. A tissue culture-based competition assay demonstrated that the HBD effectively competes with VEGF(165) for aptamer binding in vivo. Comparison of NMR spectra revealed that structural features of the smaller HBD-aptamer complex are present in the full-length VEGF(164)-aptamer complex. These data show that the HBD provides the binding site for the aptamer and is the primary determinant for the affinity and specificity in the VEGF(165)-aptamer complex.
journal_name
Proc Natl Acad Sci U S Aauthors
Lee JH,Canny MD,De Erkenez A,Krilleke D,Ng YS,Shima DT,Pardi A,Jucker Fdoi
10.1073/pnas.0509069102keywords:
subject
Has Abstractpub_date
2005-12-27 00:00:00pages
18902-7issue
52eissn
0027-8424issn
1091-6490pii
0509069102journal_volume
102pub_type
杂志文章abstract::This article emphasizes the role played by a remarkable pointwise inequality satisfied by fractionary derivatives in order to obtain maximum principles and Lp-decay of solutions of several interesting partial differential equations. In particular, there are applications to quasigeostrophic flows, in two space variable...
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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