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Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2.

<div class='caption-title'>Stereo figure of the NOX-E36 L-aptamer·CCL2 complex.</div>
<div class='caption-title'>Structure of the NOX-E36 L-aptamer.</div>
<div class='caption-title'>Interactions between L-aptamer and CCL2.</div>
Oberthür D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C
OpenAccess logo Nat Commun 6 6923 (2015)
Cited: 46 times
EuropePMC logo PMID: 25901662

Abstract

We report the crystal structure of a 40 mer mirror-image RNA oligonucleotide completely built from nucleotides of the non-natural L-chirality in complex with the pro-inflammatory chemokine L-CLL2 (monocyte chemoattractant protein-1), a natural protein composed of regular L-amino acids. The L-oligonucleotide is an L-aptamer (a Spiegelmer) identified to bind L-CCL2 with high affinity, thereby neutralizing the chemokine's activity. CCL2 plays a key role in attracting and positioning monocytes; its overexpression in several inflammatory diseases makes CCL2 an interesting pharmacological target. The PEGylated form of the L-aptamer, NOX-E36 (emapticap pegol), already showed promising efficacy in clinical Phase II studies conducted in diabetic nephropathy patients. The structure of the L-oligonucleotide[Symbol: see text]L-protein complex was solved and refined to 2.05 Å. It unveils the L-aptamer's intramolecular contacts and permits a detailed analysis of its structure-function relationship. Furthermore, the analysis of the intermolecular drug-target interactions reveals insight into the selectivity of the L-aptamer for certain related chemokines.

Reviews - 4r8i mentioned but not cited (1)

  1. Structural Biology for the Molecular Insight between Aptamers and Target Proteins. Zhang N, Chen Z, Chen Z, Liu D, Jiang H, Zhang ZK, Lu A, Zhang BT, Yu Y, Zhang G. Int J Mol Sci 22 4093 (2021)

Articles - 4r8i mentioned but not cited (2)

  1. Crystal structure of a mirror-image L-RNA aptamer (Spiegelmer) in complex with the natural L-protein target CCL2. Oberthür D, Achenbach J, Gabdulkhakov A, Buchner K, Maasch C, Falke S, Rehders D, Klussmann S, Betzel C. Nat Commun 6 6923 (2015)
  2. Energy Transfer as A Driving Force in Nucleic Acid⁻Protein Interactions. Zavyalova E, Kopylov A. Molecules 24 (2019)


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  1. Aptamers as targeted therapeutics: current potential and challenges. Zhou J, Rossi J. Nat Rev Drug Discov 16 181-202 (2017)
  2. Liver macrophages in tissue homeostasis and disease. Krenkel O, Tacke F. Nat. Rev. Immunol. 17 306-321 (2017)
  3. Mechanisms of Regulation of the Chemokine-Receptor Network. Stone MJ, Hayward JA, Huang C, E Huma Z, Sanchez J. Int J Mol Sci 18 (2017)
  4. Embracing proteins: structural themes in aptamer-protein complexes. Gelinas AD, Davies DR, Janjic N. Curr. Opin. Struct. Biol. 36 122-132 (2016)
  5. Targeting inflammation in diabetic kidney disease: early clinical trials. Perez-Gomez MV, Sanchez-Niño MD, Sanz AB, Zheng B, Martín-Cleary C, Ruiz-Ortega M, Ortiz A, Fernandez-Fernandez B. Expert Opin Investig Drugs 25 1045-1058 (2016)
  6. Aptamers in Therapeutics. Parashar A. J Clin Diagn Res 10 BE01-6 (2016)
  7. Bacterial Heat Shock Protein Activity. Maleki F, Khosravi A, Nasser A, Taghinejad H, Azizian M. J Clin Diagn Res 10 BE01-3 (2016)
  8. The notorious R.N.A. in the spotlight - drug or target for the treatment of disease. Reautschnig P, Vogel P, Stafforst T. RNA Biol 14 651-668 (2017)
  9. MIPs and Aptamers for Recognition of Proteins in Biomimetic Sensing. Menger M, Yarman A, Erdőssy J, Yildiz HB, Gyurcsányi RE, Scheller FW. Biosensors (Basel) 6 (2016)
  10. Aptamers in the Therapeutics and Diagnostics Pipelines. Kaur H, Bruno JG, Kumar A, Sharma TK. Theranostics 8 4016-4032 (2018)
  11. Emerging therapeutics for the treatment of diabetic nephropathy. Brenneman J, Hill J, Pullen S. Bioorg. Med. Chem. Lett. 26 4394-4402 (2016)
  12. Aptamers: A Feasible Technology in Cancer Immunotherapy. Soldevilla MM, Villanueva H, Pastor F. J Immunol Res 2016 1083738 (2016)
  13. Expected and unexpected features of protein-binding RNA aptamers. Bjerregaard N, Andreasen PA, Dupont DM. Wiley Interdiscip Rev RNA 7 744-757 (2016)
  14. Using Genome Sequence to Enable the Design of Medicines and Chemical Probes. Angelbello AJ, Chen JL, Childs-Disney JL, Zhang P, Wang ZF, Disney MD. Chem. Rev. 118 1599-1663 (2018)
  15. Aptamer-iRNAs as Therapeutics for Cancer Treatment. Soldevilla MM, Meraviglia-Crivelli de Caso D, Menon AP, Pastor F. Pharmaceuticals (Basel) 11 (2018)
  16. Aptamers, the Nucleic Acid Antibodies, in Cancer Therapy. Fu Z, Xiang J. Int J Mol Sci 21 (2020)
  17. RNA Therapeutics - Research and Clinical Advancements. Feng R, Patil S, Zhao X, Miao Z, Qian A. Front Mol Biosci 8 710738 (2021)
  18. Stop chronic kidney disease progression: Time is approaching. Sharaf El Din UA, Salem MM, Abdulazim DO. World J Nephrol 5 258-273 (2016)
  19. Aptamer-guided extracellular vesicle theranostics in oncology. Tran PH, Xiang D, Nguyen TN, Tran TT, Chen Q, Yin W, Zhang Y, Kong L, Duan A, Chen K, Sun M, Li Y, Hou Y, Zhu Y, Ma Y, Jiang G, Duan W. Theranostics 10 3849-3866 (2020)
  20. Nanoparticles-Based Oligonucleotides Delivery in Cancer: Role of Zebrafish as Animal Model. Bozzer S, Bo MD, Toffoli G, Macor P, Capolla S. Pharmaceutics 13 1106 (2021)
  21. The prospect of tumor microenvironment-modulating therapeutical strategies. Eulberg D, Frömming A, Lapid K, Mangasarian A, Barak A. Front Oncol 12 1070243 (2022)
  22. Current Advances in RNA Therapeutics for Human Diseases. Zogg H, Singh R, Ro S. Int J Mol Sci 23 2736 (2022)
  23. Advances in Therapeutic L-Nucleosides and L-Nucleic Acids with Unusual Handedness. Dantsu Y, Zhang Y, Zhang W. Genes (Basel) 13 46 (2021)
  24. Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders. Basu D, Chakraborty S, Pal R, Sharma TK, Sarkar S. Int J Mol Sci 22 9661 (2021)
  25. Role of CCL2/CCR2 axis in the pathogenesis of COVID-19 and possible Treatments: All options on the Table. Ranjbar M, Rahimi A, Baghernejadan Z, Ghorbani A, Khorramdelazad H. Int Immunopharmacol 113 109325 (2022)
  26. Structural Insights into Protein-Aptamer Recognitions Emerged from Experimental and Computational Studies. Troisi R, Balasco N, Autiero I, Vitagliano L, Sica F. Int J Mol Sci 24 16318 (2023)

Articles citing this publication (17)

  1. Chemokine (C-C motif) receptor 2-positive monocytes aggravate the early phase of acetaminophen-induced acute liver injury. Mossanen JC, Krenkel O, Ergen C, Govaere O, Liepelt A, Puengel T, Heymann F, Kalthoff S, Lefebvre E, Eulberg D, Luedde T, Marx G, Strassburg CP, Roskams T, Trautwein C, Tacke F. Hepatology 64 1667-1682 (2016)
  2. Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor. Kahsai AW, Wisler JW, Lee J, Ahn S, Cahill Iii TJ, Dennison SM, Staus DP, Thomsen AR, Anasti KM, Pani B, Wingler LM, Desai H, Bompiani KM, Strachan RT, Qin X, Alam SM, Sullenger BA, Lefkowitz RJ. Nat. Chem. Biol. 12 709-716 (2016)
  3. Structural basis for specific inhibition of Autotaxin by a DNA aptamer. Kato K, Ikeda H, Miyakawa S, Futakawa S, Nonaka Y, Fujiwara M, Okudaira S, Kano K, Aoki J, Morita J, Ishitani R, Nishimasu H, Nakamura Y, Nureki O. Nat. Struct. Mol. Biol. 23 395-401 (2016)
  4. Biostable L-DNAzyme for Sensing of Metal Ions in Biological Systems. Cui L, Peng R, Fu T, Zhang X, Wu C, Chen H, Liang H, Yang CJ, Tan W. Anal. Chem. 88 1850-1855 (2016)
  5. A Detailed Protein-SELEX Protocol Allowing Visual Assessments of Individual Steps for a High Success Rate. Wang T, Yin W, AlShamaileh H, Zhang Y, Tran PH, Nguyen TN, Li Y, Chen K, Sun M, Hou Y, Zhang W, Zhao Q, Chen C, Zhang PZ, Duan W. Hum Gene Ther Methods 30 1-16 (2019)
  6. Aptamer-based liposomes improve specific drug loading and release. Plourde K, Derbali RM, Desrosiers A, Dubath C, Vallée-Bélisle A, Leblond J. J Control Release 251 82-91 (2017)
  7. Structural basis for IL-1α recognition by a modified DNA aptamer that specifically inhibits IL-1α signaling. Ren X, Gelinas AD, von Carlowitz I, Janjic N, Pyle AM. Nat Commun 8 810 (2017)
  8. Cu-Au alloy nanostructures coated with aptamers: a simple, stable and highly effective platform for in vivo cancer theranostics. Ye X, Shi H, He X, Yu Y, He D, Tang J, Lei Y, Wang K. Nanoscale 8 2260-2267 (2016)
  9. Systematic optimization and modification of a DNA aptamer with 2'-O-methyl RNA analogues. Maio G, Enweronye O, Zumrut HE, Batool S, Van N, Mallikaratchy P. ChemistrySelect 2 2335-2340 (2017)
  10. RNA Aptamers Recognizing Murine CCL17 Inhibit T Cell Chemotaxis and Reduce Contact Hypersensitivity In Vivo. Fülle L, Steiner N, Funke M, Gondorf F, Pfeiffer F, Siegl J, Opitz FV, Haßel SK, Erazo AB, Schanz O, Stunden HJ, Blank M, Gröber C, Händler K, Beyer M, Weighardt H, Latz E, Schultze JL, Mayer G, Förster I. Mol. Ther. 26 95-104 (2018)
  11. Specific suppression of D-RNA G-quadruplex-protein interaction with an L-RNA aptamer. Umar MI, Kwok CK. Nucleic Acids Res 48 10125-10141 (2020)
  12. Spiegelmer-Based Sandwich Assay for Cardiac Troponin I Detection. Tolnai ZJ, András J, Szeitner Z, Percze K, Simon LF, Gyurcsányi RE, Mészáros T. Int J Mol Sci 21 (2020)
  13. A Fiber-Based SPR Aptasensor for the In Vitro Detection of Inflammation Biomarkers. Hua Y, Wang R, Li D. Micromachines (Basel) 13 1036 (2022)
  14. De novo sequencing of highly modified therapeutic oligonucleotides by hydrophobic tag sequencing coupled with LC-MS. Goto R, Miyakawa S, Inomata E, Takami T, Yamaura J, Nakamura Y. J Mass Spectrom 52 78-93 (2017)
  15. Delivery of Cell-Specific Aptamers to the Arterial Wall with an Occlusion Perfusion Catheter. Udofot O, Lin LH, Thiel WH, Erwin M, Turner E, Miller FJ, Giangrande PH, Yazdani SK. Mol Ther Nucleic Acids 16 360-366 (2019)
  16. Elucidating the Molecular Interactions of Chemokine CCL2 Orthologs with Flavonoid Baicalin. Joshi N, Kumar D, Poluri KM. ACS Omega 5 22637-22651 (2020)
  17. Hydroxyl Groups on Annular Ring-B Dictate the Affinities of Flavonol-CCL2 Chemokine Binding Interactions. Joshi N, Tripathi DK, Nagar N, Poluri KM. ACS Omega 6 10306-10317 (2021)


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