Vascular endothelial growth factor aptamer



Description

Janjić, N. et al. reported aptamers with affinity for VEGF in their article published in 1995. The 24A aptamer was named by Janjić, N. et al. in the article[1].



SELEX

In their work published in 1995, Janjić, N. et al. used SELEX to isolate RNA aptamer sequences with affinity for VEGF from a nucleic acid library containing about 6×1014 sequences after 11 rounds of selection process. 79 unique-sequence isolates were identified from the affinity-enriched pools. These isolates were subsequently screened for VPF/VEGF binding affinity using a nitrocellulose filter binding assay, quantifying RNA-ligand interactions across a range of VPF/VEGF concentrations[1].

Detailed information are accessible on SELEX page.



Structure

The 2D structure of the figure is based on the article by online secondary structure prediction tool to draw. The figure shows the secondary structure prediction of the original aptamer sequence. This aptamer with a simple structure consists of a stem loop containing one bulge[1].

5'-ACCCUGAUGGUAGACGCCGGGGUG-3'

drawing

Ligand information

SELEX ligand

VEGF active in angiogenesis, vasculogenesis and endothelial cell growth. VEGF induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. VEGF binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin. VEGF also binds to the NRP1/neuropilin-1 receptor. Binding to NRP1 initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). VEGF also binds the DEAR/FBXW7-AS1 receptor.-----From Uniprot

UniProt ID: uniquely identifies protein sequences in the UniProt database, a resource for protein information.

Pfam: a widely recognised database of protein families and domains.

GenBank: maintained by NCBI(National Center for Biotechnology Information), is a database of nucleotide sequences from various organisms, vital for genetic and molecular biology research.

Mass: an intrinsic property of a body.

Name Uniprot ID Pfam Mass Protein sequence PDB ID GenBank
VEGF P49767 P49767 46.883 kDa
...... MHLLGFFSVACSLLAAALLPGPREAPAAAAAFESGLDLSDAEPDAGEATAYASKDLEEQLRSVSSVDELMTVLYPEYWKMYKCQLRKGGWQHNREQANLNSRTEETIKFAAAHYNTEILKSIDNEWRKTQCMPREVCIDVGKEFGVATNTFFKPPCVSVYRCGGCCNSEGLQCMNTSTSYLSKTLFEITVPLSQGPKPVTISFANHTSCRCMSKLDVYRQVHSIIRRSLPATLPQCQAANKTCPTNYMWNNHICRCLAQEDFMFSSDAGDDSTDGFHDICGPNKELDEETCQCVCRAGLRPASCGPHKELDRNSCQCVCKNKLFPSQCGANREFDENTCQCVCKRTCPRNQPLNPGKCACECTESPQKCLLKGKKFHHQTCSCYRRPCTNRQKACEPGFSYSEEVCRCVPSYWKRPQMS
2X1X
4BSK
7424

Some isolated sequences bind to the affinity of the protein[1].

Name Sequence Ligand Affinity
NX-213 5'-ACCCUGAUGGUAGACGCCGGGGUG-3' NA 0.14 ± 0.01 nM
NX-178 5'-ACCCUGAUGGUAGACGCCGGGGUG-3' NA 2.4 ± 0.5 nM
NX-191 5'-ACCCUGAUGGUAGACGCCGGGGUG-3' NA 250 ± 130 nM
NX-223 5'-ACCCUGAUGGUAGACGCCGGGGUG-3' NA 250 ± 100 nM
NX-224 5'-ACCCUGAUGGUAGACGCCGGGGUG-3' NA 320 ±70 nM
drawing

Similar compound(s)

We used the Dail server website to compare the structural similarities of ligand proteins, and chose the top 10 in terms of similarity for presentation.

Dail server website: a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB).

Z-score: a standard score that is converted from an original score. The list of neighbours is sorted by Z-score. Similarities with a Z-score lower than 2 are spurious.

RMSD: (Root Mean Square Deviation) is used to measure the degree to which atoms deviate from the alignment position.

PDB: PDB ID+ chain name.

PDB Z-socre RMSD (Å) Description
4BSK-A 29.4 0 Original chain
2XV7-A 12.6 1.5 Vascular endothelial growth factor D
1FZV-b 10.9 3.0 Placenta growth factor
2GNN-C 10.4 3.9 Vascular endothelial growth factor homolog
3MJK-A 9.4 3.3 Platelet-derived growth factor subunit A
4NT5-A 6.6 2.7 Von willebrand factor
5BPU-A 6.0 3.4 Norrin
8END-A 6.0 3.1 Bursicon
2ASK-A 5.7 3.3 Artemin
4MQW-B 5.5 2.1 Glycoprotein hormones, alpha polypeptide
8I2G-Y 5.3 2.2 Chimera of guanine nucleotide-binding protein g(s


References

[1] Nuclease-resistant nucleic acid ligands to vascular permeability factor/vascular endothelial growth factor.
Green, L. S., Jellinek, D., Bell, C., Beebe, L. A., Feistner, B. D., Gill, S. C., Jucker, F. M., & Janjić, N.
Chemistry & biology, 2(10), 683–695. (1995)