Enantioselective induction by G-quadruplex DNA/hemin in intramolecular cyclopropanation

doi:10.1016/S1872-2067(25)64797-8

Abstract

Abstract:

G-quadruplex DNA (G4) can function as a kind of nucleic acid apoenzyme for constructing G4/hemin biocatalyst to mimic the catalytic function of hemoprotein. However, achieving stereoselective control with G4/hemin remains a persistent challenge. Here, we report that a PW17/hemin (PW17: 5’-GGGTAGGGCGGGTTGGG-3’), adopting the 5’-5’ stacked dimeric parallel G4 topology, can realize the enantioselective induction in intramolecular cyclopropanation of allyl diazoacetates with enantioselectivity up to 87% ee. Spectroscopic characterization and catalytic results demonstrate that the relatively open G-quartet of the 3’ terminal in dimeric PW17 contributes a catalytic pocket for hemin accommodation and plays a pivotal role in enantioselective control. This finding expands the unique repertoire of heme enzyme using biological scaffolds from proteins to nucleic acids and resolves the long-standing challenge of stereochemical control in G4/hemin catalysis.

Key words: G-quadruplex DNA, Hemin, Enantioselectivity, Intramolecular cyclopropanation, Nucleic acid catalysis

Wenhui Miao, Jingya Hao, Wenqin Zhou, Guoqing Jia, Can Li. Enantioselective induction by G-quadruplex DNA/hemin in intramolecular cyclopropanation[J]. Chinese Journal of Catalysis, 2025, 78: 138-143.

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URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(25)64797-8

https://www.cjcatal.com/EN/Y2025/V78/I11/138

Figures/Tables 6

Scheme 1. Schematic representation of the non-covalent assembly of G-quadruplex (G4) and hemin into a G4/hemin complex and the benchmark reaction of G4/hemin catalyzed intramolecular cyclopropanation.

Fig. 1. The relationship between the enantioselectivity of product 2a and three types of G4s’ secondary structures (parallel, hybrid, and anti-parallel). The Y-axis lists the 49 G4s used in this study. The detailed sequence information is provided in Table S1.

Fig. 2. Characterization of PW17 and its complex with hemin. (a) CD spectra. (b) UV melting experiments. (c) Native polyacrylamide gel electrophoresis (PAGE), single-stranded dT17 and dT34, containing 17nt and 34nt dT, respectively, were used as the control of random structure. (d) UV-vis titration of hemin with PW17. For (a-c), the molar ratio of PW17 to hemin was maintained as 1:1. (e) Proposed dimeric structure of the PW17/hemin.

Fig. 3. (a) The relation between base modifications of PW17 (5’-GGG TAGGG CGGG TTGGG-3’) and the enantioselectivity of 2a. (b) Dimeric structure of PW17: 5’-terminal, 3’-terminal, Loop 1 (-TA-, L1), Loop 2 (-C-, L2), Loop 3 (-TT-, L3) are indicated.

Fig. 4. Imino proton NMR spectra of G4s and their hemin complexes: (a) PW17, 2LBY, and 2LPW G4s; (b) 2LBY and 2LBY/hemin; (c) 2LPW and 2LPW/hemin.

Table 1 Activities and enantioselectivities of PW17/hemin for the intramolecular cyclopropanation.

Entry	Product	Yield (%) ^a	ee (%)^{b, c}
1	2a	48±5	62±2
2	2b	37±2	77±3
3	2c	11±6	81±5
4	2d	19±5	87±7
5	2e	19±6	76±8
6	2f	23±10	75±5
7	2g	18±3	60±2

References

[1]	S. Dey, A. Jäschke, Angew. Chem. Int. Ed., 2015, 54, 11279-11282.
[2]	P. Fournier, R. Fiammengo, A. Jäschke, Angew. Chem. Int. Ed., 2009, 48, 4426-4429.
[3]	K. Chen, Z. He, W. Xiong, C.-J. Wang, X. Zhou, Chin. Chem. Lett., 2021, 32, 1701-1704.
[4]	S. Roe, D. J. Ritson, T. Garner, M. Searle, J. E. Moses, Chem. Commun., 2010, 46, 4309.
[5]	M. Wilking, U. Hennecke, Org. Biomol. Chem., 2013, 11, 6940.
[6]	P. M. Punt, M. D. Langenberg, O. Altan, G. H. Clever, J. Am. Chem. Soc., 2021, 143, 3555-3561.
[7]	C. Wang, G. Jia, J. Zhou, Y. Li, Y. Liu, S. Lu, C. Li, Angew. Chem. Int. Ed., 2012, 51, 9352-9355.
[8]	Y. Chen, K. Onizuka, F. Nagatsugi, Bioorg. Med. Chem. Lett., 2024, 109, 129855.
[9]	S. Dey, C. L. Rühl, A. Jäschke, Chem. Eur. J., 2017, 23, 12162-12170.
[10]	H. Zhao, K. Shen, Biotechnol. Prog., 2016, 32, 891-898.
[11]	J. Hao, W. Miao, Y. Cheng, S. Lu, G. Jia, C. Li, ACS Catal., 2020, 10, 6561-6567.
[12]	J. Hao, W. Miao, S. Lu, Y. Cheng, G. Jia, C. Li, Chem. Sci., 2021, 12, 7918-7923.
[13]	M. Cheng, Y. Li, J. Zhou, G. Jia, S.-M. Lu, Y. Yang, C. Li, Chem. Commun., 2016, 52, 9644-9647.
[14]	S. Dey, A. Jäschke, Molecules, 2020, 25, 3121.
[15]	C. Festa, V. Esposito, D. Benigno, S. De Marino, A. Zampella, A. Virgilio, A. Galeone, Int. J. Mol. Sci., 2022, 23, 1092.
[16]	C. Wang, Y. Li, G. Jia, Y. Liu, S. Lu, C. Li, Chem. Commun., 2012, 48, 6232-6234.
[17]	Z. Wang, X. Dong, Y. Chen, C. Wang, ChemBioChem, 2025, 26, e202400909.
[18]	F. P. Guengerich, ACS Catal., 2018, 8, 10964-10976.
[19]	S. W. Ryter, R. M. Tyrrell, Free. Radic. Biol. Med., 2000, 28, 289-309.
[20]	T. Shimizu, A. Lengalova, V. Martínek, M. Martínková, Chem. Soc. Rev., 2019, 48, 5624-5657.
[21]	D. Zhang, J. Han, Y. Li, L. Fan, X. Li, J. Phys. Chem. B, 2016, 120, 6606-6611.
[22]	D. M. Carminati, J. Decaens, S. Couve-Bonnaire, P. Jubault, R. Fasan, Angew. Chem. Int. Ed., 2021, 60, 7072-7076.
[23]	K. Chen, X. Huang, S. B. Jennifer Kan, R. K. Zhang, F. H. Arnold, Science, 2018, 360, 71-75.
[24]	P. S. Coelho, E. M. Brustad, A. Kannan, F. H. Arnold, Science, 2013, 339, 307-310.
[25]	N. S. Sarai, B. J. Levin, J. M. Roberts, D. E. Katsoulis, F. H. Arnold, ACS Cent. Sci., 2021, 7, 944-953.
[26]	S. B. Jennifer Kan, R. D. Lewis, K. Chen, F. H. Arnold, Science, 2016, 354, 1048-1051.
[27]	S. B. Jennifer Kan, X. Huang, Y. Gumulya, K. Chen, F. H. Arnold, Nature, 2017, 552, 132-136.
[28]	K. Chen, X. Huang, S.-Q. Zhang, A. Zhou, S. B. Jennifer Kan, X. Hong, F. Arnold, Synlett, 2019, 30, 378-382.
[29]	C. K. Prier, R. K. Zhang, A. R. Buller, S. Brinkmann-Chen, F. H. Arnold, Nat. Chem., 2017, 9, 629-634.
[30]	R. K. Zhang, K. Chen, X. Huang, L. Wohlschlager, H. Renata, F. H. Arnold, Nature, 2019, 565, 67-72.
[31]	H. Alwaseem, S. Giovani, M. Crotti, K. Welle, C. T. Jordan, S. Ghaemmaghami, R. Fasan, ACS Cent. Sci., 2021, 7, 841-857.
[32]	A. Z. Zhou, K. Chen, F. H. Arnold, ACS Catal., 2020, 10, 5393-5398.
[33]	D. A. Vargas, X. Ren, A. Sengupta, L. Zhu, S. Roy, M. Garcia-Borràs, K. N. Houk, R. Fasan, Nat. Chem., 2024, 16, 817-826.
[34]	J. Zhang, A. O. Maggiolo, E. Alfonzo, R. Mao, N. J. Porter, N. M. Abney, F. H. Arnold, Nat. Catal., 2023, 6, 152-160.
[35]	P. Travascio, Y. Li, D. Sen, Chem. Biol., 1998, 5, 505-517.
[36]	J. Chen, Y. Guo, J. Zhou, H. Ju, Chem. Eur. J., 2017, 23, 4210-4215.
[37]	D.-M. Kong, J. Xu, H.-X. Shen, Anal. Chem., 2010, 82, 6148-6153.
[38]	T. Ai, Q. Yang, Y. Lv, Y. Huang, Y. Li, J. Geng, D. Xiao, C. Zhou, Chem. Asian J., 2018, 13, 1805-1810.
[39]	W. Zhou, R. Lai, Y. Cheng, Y. Bao, W. Miao, X. Cao, G. Jia, G. Li, C. Li, ACS Catal., 2023, 13, 4330-4338.
[40]	R. I. Adeoye, D. S. Osalaye, T. K. Ralebitso-Senior, A. Boddis, A. J. Reid, A. A. Fatokun, A. K. Powell, S. O. Malomo, F. J. Olorunniji, Catalysts, 2019, 9, 613.
[41]	J. Kosman, K. Żukowski, B. Juskowiak, Molecules, 2018, 23, 1400.
[42]	C. Lu, M. Zandieh, J. Zheng, J. Liu, Nanoscale, 2023, 15, 8189-8196.
[43]	S. Hagiwara, A. Momotake, T. Ogura, S. Yanagisawa, A. Suzuki, S. Neya, Y. Yamamoto, Inorg. Chem., 2021, 60, 11206-11213.
[44]	J. Liu, T. Zhang, J. Feng, Y. Cui, L. Zhang, Y. Wang, M. Cui, D. Li, H. Tai, Chem. Commun., 2023, 59, 7811-7814.
[45]	B. Liu, T. Wang, D. Qiu, X. Yan, Y. Liu, J.-L. Mergny, X. Zhang, D. Monchaud, H. Ju, J. Zhou, Anal. Chem., 2024, 96, 14590-14597.
[46]	H. Ibrahim, P. Mulyk, D. Sen, ACS Omega, 2019, 4, 15280-15288.
[47]	M. Vorlíčková, I. Kejnovská, K. Bednářová, D. Renčiuk, J. Kypr, Chirality, 2012, 24, 691-698.
[48]	V. Kuryavyi, L. A. Cahoon, H. S. Seifert, D. J. Patel, Structure, 2012, 20, 2090-2102.
[49]	M. Adrian, B. Heddi, A. T. Phan, Methods, 2012, 57, 11-24.