Polímeros: Ciência e Tecnologia
Polímeros: Ciência e Tecnologia
Original Article

Adsorption of terbium ion on Fc/dymethylacrylamide: application of Monte Carlo simulation

Norma Aurea Rangel Vázquez

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The crosslinking of the Fc fragment (IgG antibody) on a polymer matrix about of dimethylacrylamide (DMA), melamide group (MG) and n-acryloxy succinimide (NAS) was analyzed through Monte Carlo simulation at 277.15K and pH 7, in where Gibs free energy and the dipole moment indicated the spontaneity of the reaction through van der Waals interactions. In addition, the QSAR properties determinated that both the surface area and the volume allow to carry out the physical adsorption of the Fc fragment that was verified through the electronic distribution of the electrostatic potential maps (MESP) where the nucleophilic zones (blue color) and electrophilic (red color) were observed, while the partition coefficient (Log P) indicated the solubility of the process. Subsequently, the analysis of the adsorption of the terbium ion (Tb+3) at 277.15K and a pH 7 in Fc/polymeric matrix was carried out, observing that the Fc fragment presented a flat-on optimization geometry attributed to the Tb+3 that generates electronic repulsions, as well as van der Waals forces, hydrogen bonds derived from the Cys aminoacids formed a polar structure and that was corroborated by the Log P negative. Finally, the surface area and volume determined that Tb+3 adsorption showed an increase in surface area and volume with temperature.


Fc, polymer, QSAR, Gibbs, Monte Carlo


1 Zielhuis, S. W., Nijsen, J. F., Seppenwoolde, J. H., Zonnenberg, B. A., Bakker, C. J., Hennink, W. E., Van Rijk, P. P., & Van Het Schip, A. D. (2005). Lanthanide, bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer. Current Medicinal Chemistry. Anti-Cancer Agents, 5(3), 303-313. http://dx.doi.org/10.2174/1568011053765958. PMid:15992356.

2 Carac, A. (2017). Biological and biomedical applications of the lanthanides compounds: a mini review. Proceedings of the Romanian Academy Series B, 19(2), 69-74. Retrieved in 2020, January 9, from https://pdfs.semanticscholar.org/ad32/2bd248e0bdbf7c2576763353dd72f02ed455.pdf

3 Teo, R. D., Termini, J., & Gray, H. B. (2016). Lanthanides: applications in cancer diagnosis and therapy. Journal of Medicinal Chemistry, 59(13), 6012-6024. http://dx.doi.org/10.1021/acs.jmedchem.5b01975. PMid:26862866.

4 Yoon, M. S., Santra, M., & Ahn, K. H. (2015). Preparation of luminescent lanthanide polymers by ring-opening metathesis polymerization. Tetrahedron Letters, 56(41), 5573-5577. http://dx.doi.org/10.1016/j.tetlet.2015.08.042.

5 Zhao, Z. P., Zheng, K., Li, H. R., Zeng, C. H., Zhong, S., Ng, S. W., Zheng, Y., & Chen, Y. (2018). Structure variation and luminescence of 3d, 2d and 1d lanthanide coordination polymers with 1,3-adamantanediacetic acid. Inorganica Chimica Acta, 482, 340-346. http://dx.doi.org/10.1016/j.ica.2018.06.027.

6 Lai, X., Gao, G., Watanabe, J., Liu, H., & Shen, H. (2017). Hydrophilic polyelectrolyte multilayers improve the ELISA system: antibody enrichment and blocking free. Polymers, 9(2), 51-63. http://dx.doi.org/10.3390/polym9020051. PMid:30970737.

7 Silva, C. S. O., Baptista, R. P., Santos, A. M., Martinho, J. M. G., Cabral, J. M. S., & Taipa, M. A. (2006). Adsorption of human IgG on to poly(N-isopropylacrylamide)-based polymer particles. Biotechnology Letters, 28(24), 2019-2025. http://dx.doi.org/10.1007/s10529-006-9188-2. PMid:17021661.

8 Welch, N. G., Scoble, J. A., Muir, B. W., & Pigram, P. J. (2017). Orientation and characterization of immobilized antibodies for improved immunoassays: review. Biointerphases, 12(2), 1-13. http://dx.doi.org/10.1116/1.4978435. PMid:28301944.

9 Shmanai, V. V., Nikolayeva, T. A., Vinokurova, L. G., & Litoshka, A. A. (2001). Oriented antibody immobilization to polystyrene macrocarriers for immunoassay modified with hydrazide derivatives of poly(meth)acrylic acid. BMC Biotechnology, 1(1), 4. http://dx.doi.org/10.1186/1472-6750-1-4. PMid:11545680.

10 De Michele, C., De Los Rios, P., Foffi, G., & Piazza, F. (2016). Simulation and theory of antibody binding to crowded antigen-covered surfaces. PLoS Computational Biology, 12(3), e1004752. http://dx.doi.org/10.1371/journal.pcbi.1004752. PMid:26967624.

11 Hebditch, M., Curtis, R., & Warwicker, J. (2017). Sequence composition predicts immunoglobulin superfamily members that could share the intrinsically disordered properties of antibody ch1 domains. Scientific Reports, 7(1), 12404 . http://dx.doi.org/10.1038/s41598-017-12616-9. PMid:28963509.

12 Janeway, C. A., Travers, P., & Walport, M. J. (2001). Immunobiology: the immune system in health and disease. New York: Garland Science.

13 Hamilton, R. G. (1987). The human IgG subclasses (Doctoral dissertation). Johns Hopkins University, Baltimore, United States.

14 Saxena, A., & Wu, D. (2016). Advances in therapeutic Fc engineering-modulation of igg-associated effector functions and serum half-life. Frontiers in Immunology, 7, 580. http://dx.doi.org/10.3389/fimmu.2016.00580. PMid:28018347.

15 Gunasekaran, K., Pentony, M., Shen, M., Garrett, L., Forte, C., Woodward, A., Ng, S. B., Born, T., Retter, M., Manchulenko, K., Sweet, H., Foltz, I. N., Wittekind, M., & Yan, W. (2010). Enhacing antibody Fc heterodimer formation through electrostatic steering effects: applications to bispecific molecules and monovalent IgG. The Journal of Biological Chemistry, 285(25), 19637-19646. http://dx.doi.org/10.1074/jbc.M110.117382. PMid:20400508.

16 Zhao, J., Nussinov, R., Wu, W. J., & Ma, B. (2018). In silico methods in antibody design. Antibodies, 7(3), 22-36. http://dx.doi.org/10.3390/antib7030022. PMid:31544874.

17 Tramontano, A. (2006). The role of molecular modelling in biomedical research. FEBS Letters, 580(12), 2928-2934. http://dx.doi.org/10.1016/j.febslet.2006.04.011. PMid:16647064.

18 Choe, W., Durgannavar, T. A., & Chung, S. J. (2016). Fc-binding ligands of immunoglobulin g: an overview of high affinity proteins and peptides. Materials, 9(12), 994-1010. http://dx.doi.org/10.3390/ma9120994. PMid:28774114.

19 Lobner, E., Traxlmayr, M. W., Obinger, C., & Hasenhindl, C. (2016). Engineered IgG1-Fc-one fragment to bind them all. Immunological Reviews, 270(1), 113-131. http://dx.doi.org/10.1111/imr.12385. PMid:26864108.

20 Hou, T., Chen, K., McLaughlin, W. A., Lu, B., & Wang, W. (2006). Computational analysis and prediction of the binding motif and protein interacting partners of the Abl SH3 domain. PLoS Computational Biology, 2(1), e1. http://dx.doi.org/10.1371/journal.pcbi.0020001. PMid:16446784.

21 Winkler, J., Armano, G., Dybowski, J. N., Kuhn, O., Ledda, F., & Heider, D. (2011). Computational design of a DNA- and Fc-binding fusion protein. Advances in Bioinformatics, 2011, 457578. http://dx.doi.org/10.1155/2011/457578. PMid:21941539.

22 Yang, C., Gao, X., & Gong, R. (2018). Engineering of Fc fragments with optimized physicochemical properties implying improvement of clinical potentials for Fc-based therapeutics. Frontiers in Immunology, 8, 1860. http://dx.doi.org/10.3389/fimmu.2017.01860. PMid:29375551.

23 Castellanos, M. M., Snyder, J. A., Lee, M., Chakravarthy, S., Clark, N. J., Mcauley, A., & Curtis, J. E. (2017). Characterization of monoclonal antibody-protein antigen complexes using small-angle scattering and molecular modeling. Antibodies, 6(4), 25-44. http://dx.doi.org/10.3390/antib6040025. PMid:30364605.

24 Pellegrini, M., & Doniach, S. (1993). Computer simulation of antibody binding specificity. Proteins, 15(4), 436-444. http://dx.doi.org/10.1002/prot.340150410. PMid:8460113.

25 Wiseman, M. E., & Frank, C. W. (2012). Antibody adsorption and orientation on hydrophobic surfaces. Langmuir, 28(3), 1765-1774. http://dx.doi.org/10.1021/la203095p. PMid:22181558.

26 Freyhult, E. K., Andersson, K., & Gustafsson, M. G. (2003). Structural modeling extends QSAR analysis of antibody-lysozyme interactions to 3d-qsar. Biophysical Journal, 84(4), 2264-2272. http://dx.doi.org/10.1016/S0006-3495(03)75032-2. PMid:12668435.

27 Souza, E. S., Zaramello, L., Kuhnen, C. A., Junkes, B. S., Yunes, R. A., & Heinzen, V. E. F. (2011). Estimating the octanol/water partition coefficient for aliphatic organic compounds using semi-empirical electrotopological index. International Journal of Molecular Sciences, 12(10), 7250-7264. http://dx.doi.org/10.3390/ijms12107250. PMid:22072945.

28 Bennour, S., & Louzri, F. (2014). Study of swelling properties and thermal behavior of poly(n,n-dimethylacrylamide-co-maleic acid) based hydrogels. Advances in Chemistry, 2014, 1-10. http://dx.doi.org/10.1155/2014/147398.

29 Fifere, A., Marangoci, N., Maier, S., Coroaba, A., Maftei, D., & Pinteala, M. (2012). Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole. Beilstein Journal of Organic Chemistry, 8, 2191-2201. http://dx.doi.org/10.3762/bjoc.8.247. PMid:23365629.

30 Bivol, V. (2006). Modelling of the 3d-structure of cam:oma photopolymers by using of computational chemistry program. Romanian Journal of Physics, 51(1-2), 269-276. Retrieved in 2020, January 9, from https://pubs.rsc.org/en/content/articlelanding/2016/cp/c5cp03599f#!divAbstract

31 Holstein, P., Harris, R. K., & Say, B. J. (1997). Solid-state 19F NMR investigation of poly(vinylidene fluoride) with high-power proton decoupling. Solid State Nuclear Magnetic Resonance, 8(4), 201-206. http://dx.doi.org/10.1016/S0926-2040(97)00014-3. PMid:9373900.

32 Mazri, R., Belaidi, S., Kerassa, A., & Lanez, T. (2014). Conformational analysis, substituent effect and structure activity relationships of 16-membered macrodiolides. International Letters of Chemistry, Physics and Astronomy, 33(2), 146-167. http://dx.doi.org/10.18052/www.scipress.com/ILCPA.33.146.

33 Chen, J., Jiang, X., Carroll, S., Huang, J., & Wang, J. (2015). Theoretical and experimental investigation of thermodynamics and kinetics of thiol-michael addition reactions: a case study of reversible fluorescent probes for glutathione imaging in single cells. Organic Letters, 17(24), 5978-5981. http://dx.doi.org/10.1021/acs.orglett.5b02910. PMid:26606171.

34 Hulubei, C. (2008). Functional maleimide-based structural polymers. Revue Roumaine de Chimie, 53(9), 743-752. Retrieved in 2020, January 9, from http://revroum.lew.ro/wp-content/uploads/2008/RRCh_9_2008/Art%2002.pdf

35 Yuan, S., Li, J., Zhu, J., Volodine, A., Li, J., Zhang, G., Van Puyvelde, P., & Van der Bruggen, B. (2018). Hydrophilic nanofiltration membranes with reduced humic acid fouling fabricated from copolymers designed by introducing carboxyl groups in the pendant benzene ring. Journal of Membrane Science, 563, 655-663. http://dx.doi.org/10.1016/j.memsci.2018.06.038.

36 Marqués-Gallego, P., & De Kroon, A. I. P. M. (2014). Ligation strategies for targeting liposomal nanocarriers. BioMed Research International, 2014, 129458. http://dx.doi.org/10.1155/2014/129458. PMid:25126543.

37 Maeda, K., Finnie, C., & Svensson, B. (2004). Cy5 maleimide labelling for sensitive detection of free thiols in native protein extracts: identification of seed proteins targeted by barley thioredoxin h isoforms. The Biochemical Journal, 378(2), 497-507. http://dx.doi.org/10.1042/bj20031634. PMid:14636158.

38 Zimmermann, J. L., Nicolaus, T., Neuert, G., & Blank, K. (2010). Thiol-based, site-specific and covalent immobilization of biomolecules for single-molecule experiments. Nature Protocols, 5(6), 975-985. http://dx.doi.org/10.1038/nprot.2010.49. PMid:20448543.

39 Han, G., Chen, S. Y., Gonzalez, V. D., Zunder, E. R., Fantl, W. J., & Nolan, G. P. (2017). Atomic mass tag of bismuth-209 for increasing the immunoassay multiplexing capacity of mass cytometry. Cytometry: Part A, 91(12), 1150-1163. http://dx.doi.org/10.1002/cyto.a.23283. PMid:29205767.

40 Chalker, J. M., Bernardes, G. J., Lin, Y. A., & Davis, B. G. (2009). Chemical modification of proteins at cysteine: opportunities in chemistry and biology. Chemistry, an Asian Journal, 4(5), 630-640. http://dx.doi.org/10.1002/asia.200800427. PMid:19235822.

41 Ciborowski, P., & Silberring, J. (2016). In proteomic profiling and analytical chemistry. New York: Elsevier.

42 Ying, T., Ju, T. W., Wang, Y., Prabakaran, P., & Dimitrov, D. S. (2014). Interactions of IgG1 CH2 and CH3 domains with FcRn. Frontiers in Immunology, 5, 146. http://dx.doi.org/10.3389/fimmu.2014.00146. PMid:24765095.

43 Singh, S. N., Yadav, S., Shire, S. J., & Kalonia, D. S. (2014). Dipole-dipole interaction in antibody solutions: correlation with viscosity behavior at high concentration. Pharmaceutical Research, 31(9), 2549-2558. http://dx.doi.org/10.1007/s11095-014-1352-0. PMid:24639233.

44 Krepper, W., Satzer, P., Beyer, B. M., & Jungbauer, A. (2018). Temperature dependence of antibody adsorption in protein A affinity chromatography. Journal of Chromatography. A, 1551, 59-68. http://dx.doi.org/10.1016/j.chroma.2018.03.059. PMid:29625770.

45 Arquilla, M., Thompson, L. M., Pearlman, L. F., & Simpkins, H. (1983). Effect of platinum antitumor agents on DMA and MA investigated by terbium fluorescence. Cancer Research, 43(3), 1211-1216. PMid:6186371.

46 Vázquez-Ibar, J. L., Weinglass, A. B., & Kaback, H. R. (2002). Engineering a terbium-binding site into an integral membrane protein for luminescence energy transfer. Proceedings of the National Academy of Sciences of the United States of America, 99(6), 3487-3492. http://dx.doi.org/10.1073/pnas.052703599. PMid:11891311.

47 Ravi, S., Krishnamurthy, V. R., Caves, J. M., Haller, C. A., & Chaikof, E. L. (2012). Maleimide-thiol coupling of a bioactive peptide to an elastin-like protein polymer. Acta Biomaterialia, 8(2), 627-635. http://dx.doi.org/10.1016/j.actbio.2011.10.027. PMid:22061108.

48 Nanda, J. S., & Lorsch, J. R. (2014). Laboratory Methods in Enzymology: protein. Part A: methods in enzymology. London: Elsevier.

49 Bulaj, G., Kortemme, T., & Goldenberg, D. P. (1998). Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry, 37(25), 8965-8972. http://dx.doi.org/10.1021/bi973101r. PMid:9636038.

50 Kogan, S., Zeng, Q., Ash, N., & Greenes, R. A. (2001). Problems and challenges in patient information retrieval: a descriptive study. Proceedings - AMIA Symposium, 2001, 329-333. PMid:11825205.

51 Ionescu, R. M., Vlasak, J., Price, C., & Kirchmeier, M. (2008). Contribution of variable domains to the stability of humanized IgG1 monoclonal antibodies. Journal of Pharmaceutical Sciences, 97(4), 1414-1426. http://dx.doi.org/10.1002/jps.21104. PMid:17721938.

52 Hess, B., & Van der Vegt, N. F. A. (2006). Hydration thermodynamic properties of amino acid analogues: a systematic comparison of biomolecular force fields and water models. The Journal of Physical Chemistry B, 110(35), 17616-17626. http://dx.doi.org/10.1021/jp0641029. PMid:16942107.

53 Ning, L., Zhang, L., Hu, L., Yang, F., Duan, C., & Zhang, Y. (2011). DFT calculations of crystal-field parameters for the lanthanide ions in the LaCl3 crystal. Journal of Physics Condensed Matter, 23(20), 205502. http://dx.doi.org/10.1088/0953-8984/23/20/205502. PMid:21540498.

54 Rzączyńska, Z., Woźniak, M., Wołodkiewicz, W., Ostasz, A., & Pikus, S. (2007). Thermal properties of lanthanide(III) complexes with 5-amino-1,3-benzenedicarboxylic acid. Journal of Thermal Analysis and Calorimetry, 88(3), 871-876. http://dx.doi.org/10.1007/s10973-005-7463-4.

55 Beck, A., Goetsch, L., Dumontet, C., & Corvaïa, N. (2017). Strategies and challenges for the next generation of antibody-drug conjugates. Nature Reviews. Drug Discovery, 16(5), 315-337. http://dx.doi.org/10.1038/nrd.2016.268. PMid:28303026.

56 Kanmert, D. (2011). Structure and interactions of human IgG-Fc (Thesis dissertation). Linkoping University, Linkoping, Sweden.

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