Catalytic, theoretical, and biological investigation of an enzyme mimic model

Artificial catalyst studies were always stayed at the kinetics investigation level, in this work bioactivity of designed catalyst were shown by the induction of biomineralization of the cells, indicating the possible use of enzyme mimics for biological applications. The development of artificial enzymes is a continuous quest for the development of tailored catalysts with improved activity and stability. Understanding the catalytic mechanism is a replaceable step for catalytic studies and artificial enzyme mimics provide an alternative way for catalysis and a better understanding of catalytic pathways at the same time. Here we designed an artificial catalyst model by decorating peptide nanofibers with a covalently conjugated catalytic triad sequence. Owing to the self-assembling nature of the peptide amphiphiles, multiple action units can be presented on the surface for enhanced catalytic performance. The designed catalyst has shown an enzyme-like kinetics profile with a significant substrate affinity. The cooperative action in between catalytic triad amino acids has shown improved catalytic activity in comparison to only the histidine-containing control group. Histidine is an irreplaceable contributor to catalytic action and this is an additional reason for control group selection. This new method based on the self-assembly of covalently conjugated action units offers a new platform for enzyme investigations and their further applications. Artificial catalyst studies always stayed at the kinetics investigation level, in this work bioactivity of the designed catalyst was shown by the induction of biomineralization of the cells, indicating the possible use of enzyme mimics for biological applications.

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1. Zhou Z, Roelfes G. Synergistic catalysis in an artificial enzyme by simultaneous action of two abiological catalytic sites. Nature Catalysis 2020; 3 (3): 289-294. doi: 10.1038/s41929-019-0420-6
2. Lin S, Wu J, Yao J, Cao W, Muhammad F, Wei H. Chapter 7 - Nanozymes for Biomedical Sensing Applications: From In Vitro to Living Systems. In : Sarmento B, das Neves J, editors. Biomedical Applications of Functionalized Nanomaterials: Elsevier 2018; pp. 171-209.
3. Kuah E, Toh S, Yee J, Ma Q, Gao Z. Enzyme mimics: advances and applications. Chemistry 2016; 22 (25): 8404-8430. doi: 10.1002/ chem.201504394
4. Shoda S-i, Uyama H, Kadokawa J-i, Kimura S, Kobayashi S. Enzymes as green catalysts for precision macromolecular synthesis. Chemical Reviews 2016; 116 (4): 2307-2413. doi: 10.1021/acs.chemrev.5b00472
5. Gulseren G, Yasa IC, Ustahuseyin O, Tekin ED, Tekinay AB et al. Alkaline phosphatase-mimicking peptide nanofibers for osteogenic differentiation. Biomacromolecules 2015; 16 (7): 2198-2208. doi: 10.1021/acs.biomac.5b00593
6. Wulff G. Enzyme-like catalysis by molecularly imprinted polymers. Chemical Reviews 2002; 102 (1): 1-28. doi: 10.1021/cr980039a
7. Tramontano A, Schloeder D. Production of antibodies that mimic enzyme catalytic activity. Methods in Enzymology. 178: Academic Press 1989. p. 531-550.
8. Lin Y, Ren J, Qu X. Nano-gold as artificial enzymes: hidden talents. Advanced Materials 2014; 26 (25): 4200-4217. doi: 10.1002/adma.201400238
9. Breslow R, Dong SD. Biomimetic reactions catalyzed by cyclodextrins and their derivatives. Chemical Reviews 1998; 98 (5): 1997-2012. doi: 10.1021/cr970011j
10. Bolon DN, Mayo SL. Enzyme-like proteins by computational design. Proceedings of the National Academy of Sciences 2001; 98 (25): 14274. doi: 10.1073/pnas.251555398
11. Rufo CM, Moroz YS, Moroz OV, Stöhr J, Smith TA et al. Short peptides self-assemble to produce catalytic amyloids. Nature Chemistry 2014; 6 (4): 303-309. doi: 10.1038/nchem.1894.
12. Gulseren G, Khalily MA, Tekinay AB, Guler MO. Catalytic supramolecular self-assembled peptide nanostructures for ester hydrolysis. Journal of Materials Chemistry B 2016; 4 (26): 4605-4611. doi: 10.1039/C6TB00795C
13. Manto MJ, Xie P, Wang C. Catalytic dephosphorylation using ceria nanocrystals. ACS Catalysis 2017; 7 (3): 1931-1938. doi: 10.1021/ acscatal.6b03472
14. Dasgupta A, Das D. Designer peptide amphiphiles: self-assembly to applications. Langmuir 2019; 35 (33): 10704-10724. doi: 10.1021/acs. langmuir.9b01837
15. Dodson G, Wlodawer A. Catalytic triads and their relatives. Trends in Biochemical Sciences 1998; 23 (9): 347-352. doi: 10.1016/s0968- 0004(98)01254-7
16. Buller AR, Townsend CA. Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad. Proceedings of the National Academy of Sciences 2013; 110 (8): E653. doi: 10.1073/pnas.1221050110
17. Nothling MD, Ganesan A, Condic-Jurkic K, Pressly E, Davalos A et al. Simple Design of an enzyme-inspired supported catalyst based on a catalytic triad. Chemistry 2017; 2 (5): 732-745. doi: 10.1016/j.chempr.2017.04.004
18. Stewart JJP. Optimization of parameters for semiempirical methods I. Method. Journal of Computational Chemistry 1989; 10 (2): 209-220. doi: 10.1002/jcc.540100208
19. Roothaan CCJ. New developments in molecular orbital theory. Reviews of Modern Physics 1951; 23 (2): 69-89. doi: 10.1103/ RevModPhys.23.69
20. Becke AD. Density-functional thermochemistry. III. The role of exact exchange. The Journal of Chemical Physics 1993; 98 (7): 5648-5652. doi: 10.1063/1.464913
21. Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B Condens Matter 1988; 37 (2): 785-789. doi: 10.1103/physrevb.37.785
22. Miehlich B, Savin A, Stoll H, Preuss H. Results obtained with the correlation energy density functionals of becke and Lee, Yang and Parr. Chemical Physics Letters 1989; 157 (3): 200-206. doi: 10.1016/0009-2614(89)87234-3
23. Ditchfield R, Hehre WJ, Pople JA. Self-consistent molecular-orbital methods. IX. an extended gaussian-type basis for molecular-orbital studies of organic molecules. The Journal of Chemical Physics 1971; 54 (2): 724-728. doi: 10.1063/1.1674902
24. Frisch MJT, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. (Gaussian, Inc., Wallingford CT).
25. GaussView V, Dennington, Roy; Keith, Todd; Millam, John. Semichem Inc., Shawnee Mission, KS,.
26. Gulseren G, Yasa IC, Ustahuseyin O, Tekin ED, Tekinay AB et al. Alkaline phosphatase-mimicking peptide nanofibers for osteogenic differentiation. Biomacromolecules 2015; 16 (7): 2198-2208. doi: 10.1021/acs.biomac.5b00593
27. Dai B, Li D, Xi W, Luo F, Zhang X et al. Tunable assembly of amyloid-forming peptides into nanosheets as a retrovirus carrier. Proceedings of the National Academy of Sciences 2015; 112 (10): 2996-3001. doi: 10.1073/pnas.1416690112
28. Brockman HL. Lipases. In: Lennarz WJ, Lane MD, editors. Encyclopedia of Biological Chemistry (Second Edition). Waltham: Academic Press; 2013. p. 729-732.
29. Allen AE, Macmillan DWC. Synergistic catalysis: a powerful synthetic strategy for new reaction development. Chemical Science 2012; 2012 (3): 633-658. doi: 10.1039/C2SC00907B
30. Patil NT, Shinde VS, Gajula B. A one-pot catalysis: the strategic classification with some recent examples. Organic & Biomolecular Chemistry 2012; 10 (2): 211-224. doi: 10.1039/C1OB06432K
31. Deng Y, Kumar S, Wang H. Synergistic–cooperative combination of enamine catalysis with transition metal catalysis. Chemical Communications 2014; 50 (33): 4272-4284. doi: 10.1039/C4CC00072B
32. Krautwald S, Schafroth MA, Sarlah D, Carreira EM. Stereodivergent α-allylation of linear aldehydes with dual iridium and amine catalysis. Journal of the American Chemical Society 2014; 136 (8): 3020-3023. doi: 10.1021/ja5003247.
33. Zhang C, Xue X, Luo Q, Li Y, Yang K et al. Self-assembled peptide nanofibers designed as biological enzymes for catalyzing ester hydrolysis. ACS Nano 2014; 8 (11): 11715-11723. doi: 10.1021/nn5051344
34. Al-Garawi ZS, McIntosh BA, Neill-Hall D, Hatimy AA, Sweet SM et al. The amyloid architecture provides a scaffold for enzyme-like catalysts. Nanoscale 2017; 9 (30): 10773-10783. doi: 10.1039/C7NR02675G
35. Rufo CM, Moroz YS, Moroz OV, Stohr J, Smith TA et al. Short peptides self-assemble to produce catalytic amyloids. Nature Chemistry 2014; 6 (4): 303-309. doi: 10.1038/nchem.1894
36. Friedmann MP, Torbeev V, Zelenay V, Sobol A, Greenwald J et al. Towards prebiotic catalytic amyloids using high throughput screening. PloS one 2015; 10 (12): e0143948. doi: 10.1371/journal.pone.0143948
37. Guler MO, Stupp SI. A self-assembled nanofiber catalyst for ester hydrolysis. Journal of the American Chemical Society 2007; 129 (40): 12082-12083. doi: 10.1021/ja075044n