hTNF α aptamer

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Timeline

Ke-Tai Guo et.al isolated aptamers that these DNA aptamers bound to hTNFalpha with high affinity[2]

Xinrui Yan et.al isolated aptamers that four 2'-NH2-modified aptamers bound to hTNFalpha with high affinity[1]

Kazem Mashayekhi et.al isolated aptamers that four aptamers with anti-hTNF-α inhibitory effect were identified[3]

Description

In 2004, Xinrui Yan and Zhang Z used the SELEX (systematic evolution of ligands by exponential enrichment) process, we isolated oligonucleotide ligands (aptamers) with high affinities for hTNFalpha. Aptamers were selected from a starting pool of 40 randomized sequences composed of about 10(15) RNA molecules[1].


SELEX

In 2004, Xinrui Yan and colleagues used existing research to design the method required for the in vitro genetic-selection. Starting from an oligonucleotide library with 40 randomized sequences, aptamers that bind specifically to TNF α were selected after 12 rounds of selection and amplification[1].
Detailed information are accessible on SELEX page.



Structure

The 2D structure of the figure is based on the prediction results of the RNA fold website by ribodraw tool to draw[1].

5'-GGGAGGACGAUGUUACGCAUCGUUUGCGUGGCGUGUCCGGGCGCAAGAAGACUCGCAAGA-3'

drawing


Ligand information

SELEX ligand

Tumor Necrosis Factor (TNF) (also known as cachectin or TNF-alpha) is a cytokine which has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; finally, it can stimulate cell proliferation and induce cell differentiation under certain conditions.-----From Pfam

Name Uniprot ID Pfam MW Amino acids sequences PDB Gene ID
hTNF α P01375 PF00229 25.644 kDa MSTESMIRDVELAEEALPKKTGGPQGSRRCLFLSLFSFLIVAGATTLFCLLHFGVIGPQREEFPRDLSLISPLAQAVRSSSRTPSDKPVAHVVANPQAEGQLQWLNRRANALLANGVELRDNQLVVPSEGLYLIYSQVLFKGQGCPSTHVLLTHTISRIAVSYQTKVNLLSAIKSPCQRETPEGAEAKPWYEPIYLGGVFQLEKGDRLSAEINRPDYLDFAESGQVYFGIIAL 1A8M 7124

The aptamer bind to the affinity of the protein.

Name Sequence Ligand Affinity
3.1 aptamer 5'-GGGAGGACGAUGUUACCCCGGGUUCUGUAUGAUCCGACCGGUCAGAUAAGACCACAAGAAGACUCGCAAGA-3' hTNF α NA
7.5 aptamer 5'-GGGAGGACGAUGUUACGCAUCGUUUGCGUGGCGUGUCCGGGCGCCGAUUCGUAAAAAGAAGACUCGCAAGA-3' hTNF α NA
12 aptamer 5'-GGGAGGACGAUGUUACUAGGCGGAUUGUUUCGAUUCUUUGCCUUGUCCCUAGUGCAAGAAGACUCGCAAGA-3' hTNF α NA
14.8 aptamer 5'-GGGAGGACGAUGUUACGUAUAUACGGAUUAGGUUGUAGCUCAGACCAGUAAUGUCAAGAAGACUCGCAAGA-3' hTNF α NA
16.3 aptamer 5'-GGGAGGACGAUGUUACGUGCUAGAUGCUACGAGUGGUCUCCUCACGUAGAAGGGGAAGAAGACUCGCAAGA-3' hTNF α NA
18.1 aptamer 5'-GGGAGGACGAUGUUAGGUCCCACAUAGGUUGGUCUUGUUGUAUGGGCUGUUUGCAAAGAAGACUCGCAAGA-3' hTNF α NA
1 aptamer 5'-GGGAGGACGAUGUUAGUGUUUUGGGAGAGAAAAGGGGGAGCCUUUACUUUGUUGGAAGAAGACUCGCAAGA-3' hTNF α NA
2 aptamer 5'-GGGAGGACGAUGUUAGACGAUGUUAUCAGGGAGUUGGGAUCAUAUAGUCUUACAUAAGAAGACUCGCAAGA-3' hTNF α NA
4 aptamer 5'-GGGAGGACGAUGUUACGCAAGAGCCGCCCUAAUGGUUCAAUGGUAACUGUAUAUGAAGAAGACUCGCAAGA-3' hTNF α NA
6 aptamer 5'-GGGAGGACGAUGUUAGACUUCUUGUGCCAUUAUGAAUUAUUGCUAAUCCUCUUGAAAGAAGACUCGCAAGA-3' hTNF α NA
8.6 aptamer 5'-GGGAGGACGAUGUUAAGGACGUACUUGGAAAAGAGGCGCGAAGAACCUGGUAUGUAAGAAGACUCGCAAGA-3' hTNF α NA
9 aptamer 5'-GGGAGGACGAUGUUAUAGGACGUACUUGGAAAAGAGGCGCGAAGAACCUGGUAUGAAGAAGACUCGCAAGA-3' hTNF α NA
10 aptamer 5'-GGGAGGACGAUGUUAUGGCCACCUUGCCACUCUUCCUUGCAUAUUUUACUCCCGCAAGAAGACUCGCAAGA-3' hTNF α NA
11.7 aptamer 5'GGGAGGACGAUGUUACAAGCCGAGGGGGAGUAUCUGAUGACAAUUCGGAGCUCCAAAGAAGACUCGCAAGA-3' hTNF α NA
13.2 aptamer 5'-GGGAGGACGAUGUUAUCAUGGUGUGUGAGUUAGCUCACGUGCCGUUUCGAAGGCGAAGAAGACUCGCAAGA-3' hTNF α NA
17.9 aptamer 5'-GGGAGGACGAUGUUACAUGGGCUAGACCGGCAUAAAACUGCUGUAGUUGCACGCCAAGAAGACUCGCAAGA-3' hTNF α NA
20.4 aptamer 5'-GGGAGGACGAUGUUACGUUGUAGUAGUGGCUUGGGCAUAACUCAGUUAAACACUAAAGAAGACUCGCAAGA-3' hTNF α NA
15 aptamer 5'-GGGAGGACGAUGUUAGACCGCGGAAAAGGAAGGAAUUAGAUACAACGGAGAAGUGAAGAAGACUCGCAAGA-3' hTNF α NA
T1.7.5 aptamer 5'-GGGAGGACGAUGUUACGCAUCGUUUGCGUGGCGUGUCCGGGCGCAAGAAGACUCGCAAGA-3' hTNF α NA
T4.14.8 aptamer 5'-GGGAGGACGAUGUUACGUAUAUACGGAUUAGGUUGUAGCUCAGACCAAGAAGACUCGCAAGA-3' hTNF α NA
drawing

Similar compound

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. The Dali server is a network service for comparing protein structures in 3D. Dali compares them against those in the Protein Data Bank (PDB). Z-score is 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) value is used to measure the degree to which atoms deviate from the alignment position.

PDB Z-socre RMSD Description
2RE9-A 18.9 2.0 Tnf Superfamily Ligand Tl1A
3URF-A 18.6 1.9 Tumor Necrosis Factor Ligand Superfamily Member 1
3QD6-D 18.1 1.8 Cd40 Ligand
7KX0-A 14.7 2.5 Cd70 Antigen
1RJ7-E 13.9 2.4 Ectodysplasin A
6MKB-B 12.1 2.4 Tumor Necrosis Factor Ligand Superfamily Member 9
5KCA-A 12.1 2.4 Cerebellin-1, Cerebellin-1, Cerebellin-1, Glutamate
4HT1-T 12.0 2.4 Tumor Necrosis Factor Ligand Superfamily Member 1
7R1M-A 12.0 2.4 Exosporium Protein
2R6Q-A 11.8 2.2 Bcla Protein


References

[1] Isolation and characterization of 2'-amino-modified RNA aptamers for human TNFalpha.
Yan X, Gao X, Zhang Z.
Genomics Proteomics Bioinformatics. 2(1):32-42. (2004)
[2] Screening and characterization of DNA aptamers with hTNF-alpha binding and neutralizing activity.
Guo KT, Yan XR, Huang GJ, Xu CX, Chai YS, Zhang ZQ.
Sheng Wu Gong Cheng Xue Bao. 19(6):730-3. (2003)
[3] Designing a new dimerized anti human TNF-α aptamer with blocking activity.
Mashayekhi K, Ganji A, Sankian M.
Biotechnol Prog. 36(4):e2969. (2020)