A9g RNA aptamer

•

横向排列的点击按钮

Timeline

2002

Lupold et al. used the extracellular part of PSMA to select an aptamer, termed A9, capable of inhibiting PSMA enzymatic activity and binding to PSMA-positive cells with low nanomolar affinity[2]

2006

The A9 aptamer, stabilized by the incorporation of 2′-fluor-pyrimidines bases, has since been used in a variety of functional studies, including the A9-mediated delivery of therapeutic siRNA to PCa cells[3]

2010

A9 apatmer is used in A9-targeted gold nanoparticles for PCa imaging and delivery of doxorubicin payloads[4]

2011

A9 aptamer was modified to prepare a minimal functional part, giving rise to A9g, its truncated 43-nucleotide variant[5]

2014

A9 apatmer is used in generation of A9-bound drug-loaded liposomes[6]

Description

 In 2002, Lupold et al. used the extracellular part of PSMA to select an aptamer, termed A9. In 2006, The A9 aptamer, stabilized by the incorporation of 2′-fluor-pyrimidines bases, has since been used in a variety of functional studies, including the A9-mediated delivery of therapeutic siRNA to PCa cells. In 2014, A9 apatmer is used in generation of A9-bound drug-loaded liposomes[2,3,6].

SELEX

Aptamers can be prepared by an in vitro selection process, termed SELEX (systematic evolution of ligands by exponential enrichment) and can be used in various biological/biotechnological settings, including the development of biomaterials , and as recognition molecules in biosensors and diagnostic, gene-regulatory, therapeutic and imaging applications[2].
Detailed information are accessible on SELEX page.



Structure

2D representation

Here we used ribodraw to complete the figure, through the 3D structure information. A9g RNA aptamer was the aptamer sequence mainly studied in SELEX article[1].

5'-GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC-3'

 drawing

3D visualisation

Ptacek J. et al.sovled the crystal structure, at 2.20 A resolution. The PDB ID of this structure is 6RTI[1].
Additional available structures that have been solved and detailed information are accessible on Structures page.

(Clicking the "Settings/Controls info" to turn Spin off)      
drawing PDBe Molstar




Binding pocket

Left: Surface representation of the binding pocket of the aptamer generated from PDB ID: 6RTI by X-ray diffraction. GCPII (shown in vacuumm electrostatics), blue is positive charge, red is negative charge. Right: The hydrogen bonds of binding sites of the aptamer bound with GCPII.

drawing drawing


Ligand information

SELEX ligand

Glutamate carboxypeptidase III (GCPIII), a close paralog of PSMA with high sequence similarity, is expressed in several human tissues. Many small-molecule ligands developed as PSMA-specific inhibitors bind to human GCPIII with nanomolar affinity , which could, in principle, hamper their use in clinical applications[1].

Name Sequence Ligand Affinity
A9g RNA aptamer 5'-GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC-3' human glutamate carboxypeptidase II (GCPII) 47nm

Structure ligand

TAH molecule, also known as N-acetyl-L-aspartyl-L-glutamate peptidase I (NAALADase I), NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 (folate hydrolase 1) gene.[3] Human GCPII contains 750 amino acids and weighs approximately 84 kDa.-----from Wikipedia
Uniprot ID Pfam MW Amino acids sequences PDB ID GenBank
Q04609 CD08022 79.53 KDa KSSNEATNITPKHNMKAFLDELKAENIKKFLYNFTQIPHLAGTEQNFQLAKQIQSQWKEFGLDSVELAHYDVLLSYPNKTHPNYISIINEDGNEIFNTSLFEPPPPGYENVSDIVPPFSAFSPQGMPEGDLVYVNYARTEDFFKLERDMKINCSGKIVIARYGKVFRGNKVKNAQLAGAKGVILYSDPADYFAPGVKSYPDGWNLPGGGVQRGNILNLNGAGDPLTPGYPANEYAYRRGIAEAVGLPSIPVHPIGYYDAQKLLEKMGGSAPPDSSWRGSLKVPYNVGPGFTGNFSTQKVKMHIHSTNEVTRIYNVIGTLRGAVEPDRYVILGGHRDSWVFGGIDPQSGAAVVHEIVRSFGTLKKEGWRPRRTILFASWDAEEFGLLGSTEWAEENSRLLQERGVAYINADSSIEGNYTLRVDCTPLMYSLVHNLTKELKSPDEGFEGKSLYESWTKKSPSPEFSGMPRISKLGSGNDFEVFFQRLGIASGRARYTKNWETNKFSGYPLYHSVYETYELVEKFYDPMFKYHLTVAQVRGGMVFELANSIVLPFDCRDYAVVLRKYADKIYSISMKHPQEMKTYSVSFDSLFSAVKNFTEIASKFSERLQDFDKSNPIVLRMMNDQLMFLERAFIDPLGLPDRPFYRHVIYAPSSHNKYAGESFPGIYDALFDIESKVDPSKAWGEVKRQIYVAAFTVQAAAETLSEVA 2OOT 9606
drawing

Similar compound

We used the Dail server website to compare the structural similarities of ligand proteins, and selected the previous information with high 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).
PDB Z-score RMSD Description
3BI0-A 64.7 0.5 Glutamate carboxypeptidase 2
6RTI-A 64.5 0 Glutamate carboxypeptidase 2
3FF3-A 60.9 0.8 Glutamate carboxypeptidase iii
4TWE-B 53.7 1.8 N-acetylated-alpha-linked acidic dipeptidase-like
6WRX-B 43.8 2.5 Transferrin receptor protein 1
1DE4-I 1DE4-I 2.5 Hemochromatosis protein
3S9L-A 42.5 2.5 Transferrin receptor protein 1
3KAS-A 40.7 2.7 Transferrin receptor protein 1
1CX8-A 40.7 2.7 Transferrin receptor protein
2NSU-A 40.6 2.7 Transferrin receptor protein 1


References

[1] Three small ribooligonucleotides with specific arginine sites.
Connell, G. J., Illangesekare, M., & Yarus, M.
Biochemistry, 32(21), 5497–5502. (1993)
[2] Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen.
Lupold, S. E., Hicke, B. J., Lin, Y., & Coffey, D. S.
Cancer research, 62(14), 4029–4033. (2002)
[3] Aptamer mediated siRNA delivery.
Chu, T. C., Twu, K. Y., Ellington, A. D., & Levy, M.
Nucleic acids research, 34(10), e73. (2006)
[4] A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer.
Kim, D., Jeong, Y. Y., & Jon, S.
ACS nano, 4(7), 3689–3696. (2010)
[5] Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling.
Rockey, W. M., Hernandez, F. J., Huang, S. Y., Cao, S., Howell, C. A., Thomas, G. S., Liu, X. Y., Lapteva, N., Spencer, D. M., McNamara, J. O., Zou, X., Chen, S. J., & Giangrande, P. H.
Nucleic acid therapeutics, 21(5), 299–314. (2011)
[6] RNA aptamer-conjugated liposome as an efficient anticancer drug delivery vehicle targeting cancer cells in vivo.
Baek, S. E., Lee, K. H., Park, Y. S., Oh, D. K., Oh, S., Kim, K. S., & Kim, D. E.
Journal of controlled release : official journal of the Controlled Release Society, 196, 234–242. (2014)
[7] Structural basis of prostate-specific membrane antigen recognition by the A9g RNA aptamer.
Ptacek, J., Zhang, D., Qiu, L., Kruspe, S., Motlova, L., Kolenko, P., Novakova, Z., Shubham, S., Havlinova, B., Baranova, P., Chen, S. J., Zou, X., Giangrande, P., & Barinka, C.
Nucleic acids research, 48(19), 11130–11145. (2020)