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Affibody molecule

December 27, 2022

Affibody molecules are small, robust proteins engineered to bind to a large number of target proteins or peptides with high affinity, imitating monoclonal antibodies, and are therefore a member of the family of antibody mimetics. Affibody molecules are used in biochemical research and are being developed as potential new biopharmaceutical drugs.[1] These molecules can be used for molecular recognition in diagnostic and therapeutic applications.[2][3]

Development

As with other antibody mimetics, the idea behind developing the Affibody molecule was to apply a combinatorial protein engineering approach on a small and robust protein scaffold. The aim was to generate new binders capable of specific binding to different target proteins with almost good affinity, while retaining the favorable folding and stability properties, and ease of bacterial expression of the parent molecule.[4][5]

The original Affibody protein scaffold was designed based on the Z domain (the immunoglobulin G binding domain) of protein A. These molecules are the newly developed class of scaffold proteins derived from the randomization of 13 amino acids located in two alpha helices involved in the binding activity of the parent protein domain. Lately, amino acids outside of the binding surface have been substituted in the scaffold to create a surface entirely different from the ancestral protein A domain.

In contrast to antibodies, Affibody molecules are composed of alpha helices and lack disulfide bridges. The parent three-helix bundle structure is currently the fastest folding protein structure known.[6] Specific Affibody molecules binding a desired target protein can be “fished out” from pools (libraries) containing billions of different variants, using phage display.

Production

Affibody molecules are based on a three-helix bundle domain, which can be expressed in soluble and proteolytically stable forms in various host cells on its own or via fusion with other protein partners.[7]

They tolerate modification and are independently folding when incorporated into fusion proteins. Head-to-tail fusions of Affibody molecules of the same specificity have proven to give avidity effects in target binding, and head-to-tail fusion of Affibody molecules of different specificities makes it possible to get bi- or multi-specific affinity proteins. Fusions with other proteins can also be created genetically[8][9] or by spontaneous isopeptide bond formation.[10] A site for site-specific conjugation is facilitated by introduction of a single cysteine at a desired position, therefore this engineered protein can be used to conjugate to radionuclides such as technetium-99m and indium-111 to visualize receptor-overexpressing tumors.[11][12]

A number of different Affibody molecules have been produced by chemical synthesis. Since they do not contain cysteines or disulfide bridges, they fold spontaneously and reversibly into the correct three-dimensional structures when the protection groups are removed after synthesis.[13][14] In some studies, temperatures above the melting temperature have been used, with retained binding properties following return to ambient conditions.[15] Cross-linked variants have been produced as well.

Properties

An Affibody molecule consists of three alpha helices with 58 amino acids and has a molar mass of about 6 kDa. A monoclonal antibody, for comparison, is 150 kDa, and a single-domain antibody, the smallest type of antigen-binding antibody fragment, 12–15 kDa.

Affibody molecules have been shown to withstand high temperatures (90 °C (194 °F)) or acidic and alkaline conditions (pH 2.5 or pH 11, respectively).[16][17][18]

Binders with an affinity of down to sub-nanomolar have been obtained from native library selections, and binders with picomolar affinity have been obtained following affinity maturation.[19] Affibodies conjugated to weak electrophiles bind their targets covalently.[20] Combination of small size, ease of engineering, high affinity and specificity makes Affibody molecules suitable alternative as monoclonal antibodies for both molecular imaging and therapeutical applications, especially for the receptor-overexpressing tumors.[21][22] These proteins are characterized by a high rate of extravasation and rapid clearance of non-bound tracer from the circulation, as well as other nonspecific compartments, when compared to antibodies and their fragments

Applications

Affibody molecules can be used for protein purification,[13] enzyme inhibition,[15] research reagents for protein capture and detection,[23][24] diagnostic imaging[19] and targeted therapy.[25] The second generation of Affibody molecule, ABY-025, binds selectively to HER2 receptors with picomolar affinity. These Affibody molecules are in clinical development for tumor diagnosis.[26][27][28][29] Anti-HER2 Affibody molecule, fused with albumin binding domain (ABD), denoted as ABY-027, labeled with Lutetium-177 provided reduction of renal and hepatic uptake of radioactivity in mice xenografts.[30] Recently, anti-ZEGFR Affibody ZEGFR:2377 labeled with technetium-99m was successfully used to visualize ZEGR expressing tumor in mice xenograft also.[31]

References

  1. ^ Frejd FY, Kim KT (2017). "Affibody molecules as engineered protein drugs". Exp Mol Med. 49 (3): e306. doi:10.1038/emm.2017.35. PMC 5382565. PMID 28336959.
  2. ^ Garousi J, Andersson K, Mitran B, Pichl ML, Ståhl S, Orlova A, Löfblom J, Tolmachev V (2016). "PET imaging of epidermal growth factor receptor expression in tumours using 89Zr-labelled ZEGFR:2377 Affibody molecules". Int J Oncol. 48 (4): 1325–1332. doi:10.3892/ijo.2016.3369. PMC 4777594. PMID 26847636 – via SPANDIDOS PUBLICATIONS.
  3. ^ Sörensen J, Sandberg D, Sandström M, Wennborg A, Feldwisch J, Tolmachev V, Åström G, Lubberink M, Garske-Román U, Carlsson J, Lindman H (2014). "First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule". J Nucl Med. 55 (5): 730–735. doi:10.2967/jnumed.113.131243. PMID 24665085.
  4. ^ Nord, K; Nilsson, J; Nilsson, B; Uhlén, M; Nygren, P-A (1995). "A combinatorial library of an α-helical bacterial receptor domain". Protein Engineering, Design and Selection. 8 (6): 601–608. doi:10.1093/protein/8.6.601. PMID 8532685.
  5. ^ Nord, K; Gunneriusson, E; Ringdahl, J; Ståhl, S; Uhlén, M; Nygren, P-A (1997). "Binding proteins selected from combinatorial libraries of an α-helical bacterial receptor domain". Nature Biotechnology. 15 (8): 772–777. doi:10.1038/nbt0897-772. PMID 9255793. S2CID 25252394.
  6. ^ Arora, P; Oas, T; Myers, J (2004). "Fast and faster: A designed variant of the B-domain of protein A folds in 3 μsec". Protein Sci. 13 (4): 847–853. doi:10.1110/ps.03541304. PMC 2280057. PMID 15044721.
  7. ^ Ståhl, S; Nygren, P-A (1997). "The use of gene fusions to protein A and protein G in immunology and biotechnology". Pathol. Biol. 45 (1): 66–76. PMID 9097850.
  8. ^ Rönnmark, J; Hansson, M; Nguyen, T; Uhlén, M; Robert, A; Ståhl, S; Nygren, P-A (2002). "Construction and characterization of affibody-Fc chimeras produced in Escherichia coli". J. Immunol. Methods. 261 (1–2): 199–211. doi:10.1016/S0022-1759(01)00563-4. PMID 11861078.
  9. ^ Rönnmark, J; Kampf, C; Asplund, A; Höiden-Guthénberg, I; Wester, K; Pontén, F; Uhlén, M; Nygren, P-A (2003). "Affibody-beta-galactosidase immunoconjugates produced as soluble fusion proteins in the Escherichia coli cytosol". J. Immunol. Methods. 281 (1–2): 149–160. doi:10.1016/j.jim.2003.06.001. PMID 14580889.
  10. ^ Veggiani, G; Nakamura, T; Brenner, M; Gayet, R; Yan, J; Robinson, C; Howarth, M (2016). "Programmable polyproteams built using twin peptide superglues". PNAS. 113 (5): 1202–1207. Bibcode:2016PNAS..113.1202V. doi:10.1073/pnas.1519214113. PMC 4747704. PMID 26787909.
  11. ^ Altai M, Wållberg H, Orlova A, Rosestedt M, Hosseinimehr SJ, Tolmachev V, Ståhl S (2012). "Order of amino acids in C-terminal cysteine-containing peptide-based chelators influences cellular processing and biodistribution of 99mTc-labeled recombinant Affibody molecules". Amino Acids. 42 (5): 1975–1985. doi:10.1007/s00726-011-0927-x. PMID 21573874. S2CID 7995180.
  12. ^ Tolmachev V, Friedman M, Sandström M, Eriksson TL, Rosik D, Hodik M, Ståhl S, Frejd FY, Orlova A (2009). "Affibody molecules for epidermal growth factor receptor targeting in vivo: aspects of dimerization and labeling chemistry". J Nucl Med. 50 (2): 274–283. doi:10.2967/jnumed.108.055525. PMID 19164241.
  13. ^ a b Nord, K; Nord, O; Uhlén, M; Kelley, B; Ljungqvist, C; Nygren, P-A (2001). "Recombinant human factor VIII-specific affinity ligands selected from phage-displayed combinatorial libraries of protein A". Eur. J. Biochem. 268 (15): 1–10. doi:10.1046/j.1432-1327.2001.02344.x. PMID 11488921.
  14. ^ Engfeldt, T; Renberg, B; Brumer, H; Nygren, P-A; Karlström, EA (2005). "Chemical synthesis of triple-labelled three-helix bundle binding proteins for specific fluorescent detection of unlabelled protein". ChemBioChem. 6 (6): 1043–1050. doi:10.1002/cbic.200400388. PMID 15880677. S2CID 5895074.
  15. ^ a b . Finnzymes. Archived from the original on 2009-03-28.
  16. ^ Ahlgren, S; Wållberg, H; Tran, TA; Widström, C; Hjertman, M; Abrahmsén, L; Berndorff, D; Dinkelborg, LM; et al. (2009). "Targeting of HER2-expressing tumors with a site-specifically 99mTc-labeled recombinant affibody molecule, ZHER2:2395, with C-terminally engineered cysteine". J. Nucl. Med. 50 (5): 781–789. doi:10.2967/jnumed.108.056929. PMID 19372467.
  17. ^ Orlova, A; Rosik, D; Sandström, M; Lundqvist, H.; Einarsson, L; Tolmachev, V (2007). "Evaluation of [(111/114m)In]CHX-A"-DTPA-ZHER2:342, an affibody ligand conjugate for targeting of HER2-expressing malignant tumors". Q. J. Nucl. Med. Mol. Imaging. 51 (4): 314–23. PMID 17464277.
  18. ^ Tran, T; Engfeldt, T; Orlova, A; Sandström, M; Feldwisch, J; Abrahmsén, L; Wennborg, A; Tolmachev, V; et al. (2007). "(99m)Tc-maEEE-Z(HER2:342), an Affibody molecule-based tracer for the detection of HER2 expression in malignant tumors". Bioconjug. Chem. 18 (6): 1956–64. doi:10.1021/bc7002617. PMID 17944527.
  19. ^ a b Orlova, A; Magnusson, M; Eriksson, TL; Nilsson, M; Larsson, B; Höidén-Guthenberg, I; Widström, C; Carlsson, J; et al. (2006). "Tumor imaging using a picomolar affinity HER2 binding affibody molecule". Cancer Res. 66 (8): 4339–48. doi:10.1158/0008-5472.CAN-05-3521. PMID 16618759.
  20. ^ Holm, L; Moody, P; Howarth, M (2009). "Electrophilic Affibodies Forming Covalent Bonds to Protein Targets". The Journal of Biological Chemistry. 284 (47): 32906–13. doi:10.1074/jbc.M109.034322. PMC 2781706. PMID 19759009.
  21. ^ Lofblom J, Feldwisch J, Tolmachev V, Carlsson J, Stahl S, Frejd FY (2010). "Affibody molecules: engineered proteins for therapeutic, diagnostic and biotechnological applications". FEBS Lett. 584 (12): 2670–2680. doi:10.1016/j.febslet.2010.04.014. PMID 20388508 – via Elsevier, Science Direct.
  22. ^ Tolmachev V, Orlova A, Nilsson FY, Feldwisch J, Wennborg A, Abrahmsen L (2007). "Affibody molecules: potential for in vivo imaging of molecular targets for cancer therapy". Expert Opin Biol Ther. 7 (4): 555–568. doi:10.1517/14712598.7.4.555. PMID 17373906. S2CID 29621968.
  23. ^ Renberg, B; Nordin, J; Merca, A; Uhlén, M; Feldwisch, J; Nygren, P-A; Karlström, AE (2007). "Affibody molecules in protein capture microarrays: evaluation of multidomain ligands and different detection formats". J. Proteome Res. 6 (1): 171–179. doi:10.1021/pr060316r. PMID 17203961.
  24. ^ Lundberg, E; Höidén-Guthenberg, I; Larsson, B; Uhlén, M; Gräslund, T (2007). "Site-specifically conjugated anti-HER2 Affibody molecules as one-step reagents for target expression analyses on cells and xenograft samples". J. Immunol. Methods. 319 (1–2): 53–63. doi:10.1016/j.jim.2006.10.013. PMID 17196217.
  25. ^ Tolmachev, V; Orlova, A; Pehrson, R; Galli, J; Baastrup, B; Andersson, K; Sandström, M; Rosik, D; et al. (2007). "Radionuclide therapy of HER2-positive microxenografts using a 177Lu-labeled HER2-specific Affibody molecule". Cancer Res. 67 (6): 2773–82. doi:10.1158/0008-5472.CAN-06-1630. PMID 17363599.
  26. ^ Feldwisch, Joachim; Tolmachev, Vladimir; Lendel, Christofer; Herne, Nina; Sjöberg, Anna; Larsson, Barbro; Rosik, Daniel; Lindqvist, Eva; Fant, Gunilla; Höidén-Guthenberg, Ingmarie; Galli, Joakim (2010-04-30). "Design of an optimized scaffold for affibody molecules". Journal of Molecular Biology. 398 (2): 232–247. doi:10.1016/j.jmb.2010.03.002. ISSN 1089-8638. PMID 20226194.
  27. ^ Gebauer, M; Skerra, A (2009). "Engineered protein scaffolds as next-generation antibody therapeutics". Current Opinion in Chemical Biology. 13 (3): 245–55. doi:10.1016/j.cbpa.2009.04.627. PMID 19501012.
  28. ^ Sörensen J, Velikyan I, Sandberg D, Wennborg A, Feldwisch J, Tolmachev V, Orlova A, Sandström M, Lubberink M, Olofsson H, Carlsson J, Lindman H (2016). "Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT". Theranostics. 6 (2): 262–271. doi:10.7150/thno.13502. PMC 4729774. PMID 26877784.
  29. ^ Sörensen J, Sandberg D, Sandström M, Wenn-borg A, Feldwisch J, Tolmachev V, Åström G, Lubberink M, Garske-Román U, Carlsson J, Lindman H (2014). "First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule" (PDF). J Nucl Med. 55 (5): 730–735. doi:10.2967/jnumed.113.131243. PMID 24665085.
  30. ^ Orlova, Anna; Jonsson, Andreas; Rosik, Daniel; Lundqvist, Hans; Lindborg, Malin; Abrahmsen, Lars; Ekblad, Caroline; Frejd, Fredrik Y.; Tolmachev, Vladimir (June 2013). "Site-specific radiometal labeling and improved biodistribution using ABY-027, a novel HER2-targeting affibody molecule-albumin-binding domain fusion protein". Journal of Nuclear Medicine. 54 (6): 961–968. doi:10.2967/jnumed.112.110700. ISSN 1535-5667. PMID 23528382. S2CID 25959793.
  31. ^ Andersson KG, Oroujeni M, Garousi J, Mitran B, Ståhl S, Orlova A, Löfblom J, Tolmachev V (2016). "Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR:2377 affibody molecule labeled with 99mTc using a peptide-based cysteine-containing chelator". Int J Oncol. 49 (6): 2285–2293. doi:10.3892/ijo.2016.3721. PMC 5118000. PMID 27748899.

External links

    December 27, 2022
    affibody, molecule, small, robust, proteins, engineered, bind, large, number, target, proteins, peptides, with, high, affinity, imitating, monoclonal, antibodies, therefore, member, family, antibody, mimetics, used, biochemical, research, being, developed, pot. Affibody molecules are small robust proteins engineered to bind to a large number of target proteins or peptides with high affinity imitating monoclonal antibodies and are therefore a member of the family of antibody mimetics Affibody molecules are used in biochemical research and are being developed as potential new biopharmaceutical drugs 1 These molecules can be used for molecular recognition in diagnostic and therapeutic applications 2 3 Contents 1 Development 2 Production 3 Properties 4 Applications 5 References 6 External linksDevelopment EditAs with other antibody mimetics the idea behind developing the Affibody molecule was to apply a combinatorial protein engineering approach on a small and robust protein scaffold The aim was to generate new binders capable of specific binding to different target proteins with almost good affinity while retaining the favorable folding and stability properties and ease of bacterial expression of the parent molecule 4 5 The original Affibody protein scaffold was designed based on the Z domain the immunoglobulin G binding domain of protein A These molecules are the newly developed class of scaffold proteins derived from the randomization of 13 amino acids located in two alpha helices involved in the binding activity of the parent protein domain Lately amino acids outside of the binding surface have been substituted in the scaffold to create a surface entirely different from the ancestral protein A domain In contrast to antibodies Affibody molecules are composed of alpha helices and lack disulfide bridges The parent three helix bundle structure is currently the fastest folding protein structure known 6 Specific Affibody molecules binding a desired target protein can be fished out from pools libraries containing billions of different variants using phage display Production EditAffibody molecules are based on a three helix bundle domain which can be expressed in soluble and proteolytically stable forms in various host cells on its own or via fusion with other protein partners 7 They tolerate modification and are independently folding when incorporated into fusion proteins Head to tail fusions of Affibody molecules of the same specificity have proven to give avidity effects in target binding and head to tail fusion of Affibody molecules of different specificities makes it possible to get bi or multi specific affinity proteins Fusions with other proteins can also be created genetically 8 9 or by spontaneous isopeptide bond formation 10 A site for site specific conjugation is facilitated by introduction of a single cysteine at a desired position therefore this engineered protein can be used to conjugate to radionuclides such as technetium 99m and indium 111 to visualize receptor overexpressing tumors 11 12 A number of different Affibody molecules have been produced by chemical synthesis Since they do not contain cysteines or disulfide bridges they fold spontaneously and reversibly into the correct three dimensional structures when the protection groups are removed after synthesis 13 14 In some studies temperatures above the melting temperature have been used with retained binding properties following return to ambient conditions 15 Cross linked variants have been produced as well Properties EditAn Affibody molecule consists of three alpha helices with 58 amino acids and has a molar mass of about 6 kDa A monoclonal antibody for comparison is 150 kDa and a single domain antibody the smallest type of antigen binding antibody fragment 12 15 kDa Affibody molecules have been shown to withstand high temperatures 90 C 194 F or acidic and alkaline conditions pH 2 5 or pH 11 respectively 16 17 18 Binders with an affinity of down to sub nanomolar have been obtained from native library selections and binders with picomolar affinity have been obtained following affinity maturation 19 Affibodies conjugated to weak electrophiles bind their targets covalently 20 Combination of small size ease of engineering high affinity and specificity makes Affibody molecules suitable alternative as monoclonal antibodies for both molecular imaging and therapeutical applications especially for the receptor overexpressing tumors 21 22 These proteins are characterized by a high rate of extravasation and rapid clearance of non bound tracer from the circulation as well as other nonspecific compartments when compared to antibodies and their fragmentsApplications EditAffibody molecules can be used for protein purification 13 enzyme inhibition 15 research reagents for protein capture and detection 23 24 diagnostic imaging 19 and targeted therapy 25 The second generation of Affibody molecule ABY 025 binds selectively to HER2 receptors with picomolar affinity These Affibody molecules are in clinical development for tumor diagnosis 26 27 28 29 Anti HER2 Affibody molecule fused with albumin binding domain ABD denoted as ABY 027 labeled with Lutetium 177 provided reduction of renal and hepatic uptake of radioactivity in mice xenografts 30 Recently anti ZEGFR Affibody ZEGFR 2377 labeled with technetium 99m was successfully used to visualize ZEGR expressing tumor in mice xenograft also 31 References Edit Frejd FY Kim KT 2017 Affibody molecules as engineered protein drugs Exp Mol Med 49 3 e306 doi 10 1038 emm 2017 35 PMC 5382565 PMID 28336959 Garousi J Andersson K Mitran B Pichl ML Stahl S Orlova A Lofblom J Tolmachev V 2016 PET imaging of epidermal growth factor receptor expression in tumours using 89Zr labelled ZEGFR 2377 Affibody molecules Int J Oncol 48 4 1325 1332 doi 10 3892 ijo 2016 3369 PMC 4777594 PMID 26847636 via SPANDIDOS PUBLICATIONS Sorensen J Sandberg D Sandstrom M Wennborg A Feldwisch J Tolmachev V Astrom G Lubberink M Garske Roman U Carlsson J Lindman H 2014 First in human molecular imaging of HER2 expression in breast cancer metastases using the 111In ABY 025 affibody molecule J Nucl Med 55 5 730 735 doi 10 2967 jnumed 113 131243 PMID 24665085 Nord K Nilsson J Nilsson B Uhlen M Nygren P A 1995 A combinatorial library of an a helical bacterial receptor domain Protein Engineering Design and Selection 8 6 601 608 doi 10 1093 protein 8 6 601 PMID 8532685 Nord K Gunneriusson E Ringdahl J Stahl S Uhlen M Nygren P A 1997 Binding proteins selected from combinatorial libraries of an a helical bacterial receptor domain Nature Biotechnology 15 8 772 777 doi 10 1038 nbt0897 772 PMID 9255793 S2CID 25252394 Arora P Oas T Myers J 2004 Fast and faster A designed variant of the B domain of protein A folds in 3 msec Protein Sci 13 4 847 853 doi 10 1110 ps 03541304 PMC 2280057 PMID 15044721 Stahl S Nygren P A 1997 The use of gene fusions to protein A and protein G in immunology and biotechnology Pathol Biol 45 1 66 76 PMID 9097850 Ronnmark J Hansson M Nguyen T Uhlen M Robert A Stahl S Nygren P A 2002 Construction and characterization of affibody Fc chimeras produced in Escherichia coli J Immunol Methods 261 1 2 199 211 doi 10 1016 S0022 1759 01 00563 4 PMID 11861078 Ronnmark J Kampf C Asplund A Hoiden Guthenberg I Wester K Ponten F Uhlen M Nygren P A 2003 Affibody beta galactosidase immunoconjugates produced as soluble fusion proteins in the Escherichia coli cytosol J Immunol Methods 281 1 2 149 160 doi 10 1016 j jim 2003 06 001 PMID 14580889 Veggiani G Nakamura T Brenner M Gayet R Yan J Robinson C Howarth M 2016 Programmable polyproteams built using twin peptide superglues PNAS 113 5 1202 1207 Bibcode 2016PNAS 113 1202V doi 10 1073 pnas 1519214113 PMC 4747704 PMID 26787909 Altai M Wallberg H Orlova A Rosestedt M Hosseinimehr SJ Tolmachev V Stahl S 2012 Order of amino acids in C terminal cysteine containing peptide based chelators influences cellular processing and biodistribution of 99mTc labeled recombinant Affibody molecules Amino Acids 42 5 1975 1985 doi 10 1007 s00726 011 0927 x PMID 21573874 S2CID 7995180 Tolmachev V Friedman M Sandstrom M Eriksson TL Rosik D Hodik M Stahl S Frejd FY Orlova A 2009 Affibody molecules for epidermal growth factor receptor targeting in vivo aspects of dimerization and labeling chemistry J Nucl Med 50 2 274 283 doi 10 2967 jnumed 108 055525 PMID 19164241 a b Nord K Nord O Uhlen M Kelley B Ljungqvist C Nygren P A 2001 Recombinant human factor VIII specific affinity ligands selected from phage displayed combinatorial libraries of protein A Eur J Biochem 268 15 1 10 doi 10 1046 j 1432 1327 2001 02344 x PMID 11488921 Engfeldt T Renberg B Brumer H Nygren P A Karlstrom EA 2005 Chemical synthesis of triple labelled three helix bundle binding proteins for specific fluorescent detection of unlabelled protein ChemBioChem 6 6 1043 1050 doi 10 1002 cbic 200400388 PMID 15880677 S2CID 5895074 a b Phusion Hot Start High Fidelity DNA Polymerase Finnzymes Archived from the original on 2009 03 28 Ahlgren S Wallberg H Tran TA Widstrom C Hjertman M Abrahmsen L Berndorff D Dinkelborg LM et al 2009 Targeting of HER2 expressing tumors with a site specifically 99mTc labeled recombinant affibody molecule ZHER2 2395 with C terminally engineered cysteine J Nucl Med 50 5 781 789 doi 10 2967 jnumed 108 056929 PMID 19372467 Orlova A Rosik D Sandstrom M Lundqvist H Einarsson L Tolmachev V 2007 Evaluation of 111 114m In CHX A DTPA ZHER2 342 an affibody ligand conjugate for targeting of HER2 expressing malignant tumors Q J Nucl Med Mol Imaging 51 4 314 23 PMID 17464277 Tran T Engfeldt T Orlova A Sandstrom M Feldwisch J Abrahmsen L Wennborg A Tolmachev V et al 2007 99m Tc maEEE Z HER2 342 an Affibody molecule based tracer for the detection of HER2 expression in malignant tumors Bioconjug Chem 18 6 1956 64 doi 10 1021 bc7002617 PMID 17944527 a b Orlova A Magnusson M Eriksson TL Nilsson M Larsson B Hoiden Guthenberg I Widstrom C Carlsson J et al 2006 Tumor imaging using a picomolar affinity HER2 binding affibody molecule Cancer Res 66 8 4339 48 doi 10 1158 0008 5472 CAN 05 3521 PMID 16618759 Holm L Moody P Howarth M 2009 Electrophilic Affibodies Forming Covalent Bonds to Protein Targets The Journal of Biological Chemistry 284 47 32906 13 doi 10 1074 jbc M109 034322 PMC 2781706 PMID 19759009 Lofblom J Feldwisch J Tolmachev V Carlsson J Stahl S Frejd FY 2010 Affibody molecules engineered proteins for therapeutic diagnostic and biotechnological applications FEBS Lett 584 12 2670 2680 doi 10 1016 j febslet 2010 04 014 PMID 20388508 via Elsevier Science Direct Tolmachev V Orlova A Nilsson FY Feldwisch J Wennborg A Abrahmsen L 2007 Affibody molecules potential for in vivo imaging of molecular targets for cancer therapy Expert Opin Biol Ther 7 4 555 568 doi 10 1517 14712598 7 4 555 PMID 17373906 S2CID 29621968 Renberg B Nordin J Merca A Uhlen M Feldwisch J Nygren P A Karlstrom AE 2007 Affibody molecules in protein capture microarrays evaluation of multidomain ligands and different detection formats J Proteome Res 6 1 171 179 doi 10 1021 pr060316r PMID 17203961 Lundberg E Hoiden Guthenberg I Larsson B Uhlen M Graslund T 2007 Site specifically conjugated anti HER2 Affibody molecules as one step reagents for target expression analyses on cells and xenograft samples J Immunol Methods 319 1 2 53 63 doi 10 1016 j jim 2006 10 013 PMID 17196217 Tolmachev V Orlova A Pehrson R Galli J Baastrup B Andersson K Sandstrom M Rosik D et al 2007 Radionuclide therapy of HER2 positive microxenografts using a 177Lu labeled HER2 specific Affibody molecule Cancer Res 67 6 2773 82 doi 10 1158 0008 5472 CAN 06 1630 PMID 17363599 Feldwisch Joachim Tolmachev Vladimir Lendel Christofer Herne Nina Sjoberg Anna Larsson Barbro Rosik Daniel Lindqvist Eva Fant Gunilla Hoiden Guthenberg Ingmarie Galli Joakim 2010 04 30 Design of an optimized scaffold for affibody molecules Journal of Molecular Biology 398 2 232 247 doi 10 1016 j jmb 2010 03 002 ISSN 1089 8638 PMID 20226194 Gebauer M Skerra A 2009 Engineered protein scaffolds as next generation antibody therapeutics Current Opinion in Chemical Biology 13 3 245 55 doi 10 1016 j cbpa 2009 04 627 PMID 19501012 Sorensen J Velikyan I Sandberg D Wennborg A Feldwisch J Tolmachev V Orlova A Sandstrom M Lubberink M Olofsson H Carlsson J Lindman H 2016 Measuring HER2 Receptor Expression In Metastatic Breast Cancer Using 68Ga ABY 025 Affibody PET CT Theranostics 6 2 262 271 doi 10 7150 thno 13502 PMC 4729774 PMID 26877784 Sorensen J Sandberg D Sandstrom M Wenn borg A Feldwisch J Tolmachev V Astrom G Lubberink M Garske Roman U Carlsson J Lindman H 2014 First in human molecular imaging of HER2 expression in breast cancer metastases using the 111In ABY 025 affibody molecule PDF J Nucl Med 55 5 730 735 doi 10 2967 jnumed 113 131243 PMID 24665085 Orlova Anna Jonsson Andreas Rosik Daniel Lundqvist Hans Lindborg Malin Abrahmsen Lars Ekblad Caroline Frejd Fredrik Y Tolmachev Vladimir June 2013 Site specific radiometal labeling and improved biodistribution using ABY 027 a novel HER2 targeting affibody molecule albumin binding domain fusion protein Journal of Nuclear Medicine 54 6 961 968 doi 10 2967 jnumed 112 110700 ISSN 1535 5667 PMID 23528382 S2CID 25959793 Andersson KG Oroujeni M Garousi J Mitran B Stahl S Orlova A Lofblom J Tolmachev V 2016 Feasibility of imaging of epidermal growth factor receptor expression with ZEGFR 2377 affibody molecule labeled with 99mTc using a peptide based cysteine containing chelator Int J Oncol 49 6 2285 2293 doi 10 3892 ijo 2016 3721 PMC 5118000 PMID 27748899 External links EditAffibody Official homepage Retrieved from https en wikipedia org w index php title Affibody molecule amp oldid 1104749706, wikipedia, wiki, book, books, library,

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