Journal ArticleDOI
Inhibition of receptor binding by high-affinity RNA ligands to vascular endothelial growth factor.
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TLDR
Oligonucleotide ligands described here represent an initial set of lead compounds in the ongoing effort toward the development of potent and specific VEGF antagonists.Abstract:
The proliferation of new blood vessels (angiogenesis) is a process that accompanies many pathological conditions including rheumatoid arthritis and solid tumor growth. Among angiogenic cytokines that have been identified to date, vascular endothelial growth factor (VEGF) is one of the most potent. We used SELEX [systematic evolution of ligands by exponential enrichment; Tuerk, C., & Gold, L. (1990) Science 249, 505-510] to identify RNA ligands that bind to VEGF in a specific manner with affinities in the low nanomolar range. Ligands were selected from a starting pool of about 10(14) RNA molecules containing 30 randomized positions. Isolates from the affinity-enriched pool were grouped into six distinct families on the basis of primary and secondary structure similarities. Minimal sequence information required for high-affinity binding to VEGF is contained in 29-36-nucleotide motifs. Binding of truncated (minimal) high-affinity ligands to VEGF is competitive with that of other truncated ligands and heparin. Furthermore, truncated ligands from the six ligand families inhibit binding of [125I]VEGF to its cell-surface receptors. Oligonucleotide ligands described here represent an initial set of lead compounds in our ongoing effort toward the development of potent and specific VEGF antagonists.read more
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Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease
Eugene W. M. Ng,David T. Shima,Perry Calias,Emmett T. Cunningham,David R. Guyer,Anthony P. Adamis +5 more
TL;DR: Pegaptanib was shown in clinical trials to be effective in treating choroidal neovascularization associated with age-related macular degeneration and has the notable distinction of being the first aptamer therapeutic approved for use in humans, paving the way for future aptamer applications.
Journal ArticleDOI
SELEX--a (r)evolutionary method to generate high-affinity nucleic acid ligands.
TL;DR: The SELEX method was modified over the years to become more efficient and less time consuming, to reach higher affinities of the aptamers selected and for automation of the process.
Journal ArticleDOI
Functional Aptamers and Aptazymes in Biotechnology, Diagnostics, and Therapy
TL;DR: Aptamers selected from chemically modified libraries can be completely resistant toward degradation by nucleases, and can lead to ligands with novel chemical functionalities normally not present in natural nucleic acids.
Journal ArticleDOI
2′-Fluoropyrimidine RNA-based Aptamers to the 165-Amino Acid Form of Vascular Endothelial Growth Factor (VEGF165) INHIBITION OF RECEPTOR BINDING AND VEGF-INDUCED VASCULAR PERMEABILITY THROUGH INTERACTIONS REQUIRING THE EXON 7-ENCODED DOMAIN
Judy Ruckman,Louis S. Green,Jim Beeson,Sheela Waugh,Wendy L. Gillette,Dwight Henninger,Lena Claesson-Welsh,Nebojsa Janjic +7 more
TL;DR: The SELEX process isolated 2′-F-pyrimidine RNA oligonucleotide ligands (aptamers) to human VEGF165, and one of the aptamers is able to significantly reduce intradermal V EGF-induced vascular permeability in vivo.
Journal ArticleDOI
Aptamers come of age – at last
TL;DR: Nucleic-acid aptamers have the molecular recognition properties of antibodies, and can be isolated robotically for high-throughput applications in diagnostics, research and therapeutics.
References
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Journal ArticleDOI
The Attractions of Proteins for Small Molecules and Ions
TL;DR: The number and variety of known compounrjs between proteins and small molecules are increasing rapidly and make a fascinating story as discussed by the authors, and there are many compounds of serum albumin, which was used during the war by many chemists, most of whom found at least one 6ew compound.
Journal ArticleDOI
Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase
Craig Tuerk,Larry Gold +1 more
TL;DR: High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species.
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In vitro selection of RNA molecules that bind specific ligands.
TL;DR: Subpopulations of RNA molecules that bind specifically to a variety of organic dyes have been isolated from a population of random sequence RNA molecules.
Journal ArticleDOI
Calculation of protein extinction coefficients from amino acid sequence data
Stanley C. Gill,P H von Hippel +1 more
TL;DR: In this article, a method for calculating accurate molar extinction coefficients for proteins at 280 nm, simply from knowledge of the amino acid composition, was presented, and the method was calibrated against 18 "normal" globular proteins.
Journal ArticleDOI
What is the evidence that tumors are angiogenesis dependent
TL;DR: Method of treating a wound or burn which comprises directly dressing its surface with non-woven fabric comprising staple fibers of spun, regenerated collagen substantially free of telopeptides is disclosed.
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