Synlett 2021; 32(04): 344-349
DOI: 10.1055/a-1290-8412
letter

Synthesis and Structural Stability of α-Helical Gold(I)-Metallopeptidesy

Lydia Zengerling
a  Department of Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
,
Benedict Kemper
a  Department of Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
,
Ute A. Hellmich
b  Department of Chemistry, Johannes Gutenberg-University Mainz, Johann-Joachim-Becher-Weg 30, 55128 Mainz, Germany
c  Centre for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt, Max-von-Laue Str. 9, 60438 Frankfurt, Germany
,
Pol Besenius
a  Department of Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
› Author Affiliations
This work was supported by the DFG (SFB 858).


Published as part of the series Thieme Chemistry Journals Awardees – Where Are They Now?

Abstract

The synthesis of hexa- and dodecapeptides functionalized with two Au(I)–phosphine complexes is reported. The high stability of the Au(I)–phosphine bond allowed orthogonal peptide-protecting-group chemistry, even when using hard Lewis acids like boron tribromide. This enabled the preparation of an Fmoc-protected lysine derivative carrying the Au(I) complex in a side chain, which was used in standard Fmoc-based solid-phase peptide synthesis protocols. Alanine and leucine repeats in the metallododecapeptide formed α-helical secondary structures in 2,2,2-trifluoroethanol–H2O and 1,1,1,3,3,3-hexafluoroisopropanol–H2O mixtures with high thermal stability, as shown by temperature-dependent CD spectroscopy studies.

Supporting Information



Publication History

Received: 16 August 2020

Accepted after revision: 15 October 2020

Publication Date:
15 October 2020 (online)

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References and Notes

  • 1 Ross NT, Katt WP, Hamilton AD. Philos. Trans. R. Soc., A 2010; 368: 989
  • 2 Milroy L.-G, Grossmann TN, Hennig S, Brunsveld L, Ottmann C. Chem. Rev. 2014; 114: 4695
  • 3 Baldwin RL. Biophys. Chem. 1995; 55: 127
  • 4 Creamer TP, Rose GD. Proc. Natl. Acad. Sci. U.S.A. 1992; 89: 5937
  • 5 Aurora R, Creamer TP, Srinivasan R, Rose GD. J. Biol. Chem. 1997; 272: 1413
  • 6 Hill RB, Raleigh DP, Lombardi A, DeGrado WF. Acc. Chem. Res. 2000; 33: 745
  • 7 Cabezas E, Satterthwait AC. J. Am. Chem. Soc. 1999; 121: 3862
  • 8 Wang D, Chen K, Kulp JL, Arora PS. J. Am. Chem. Soc. 2006; 128: 9248
  • 9 Kawamoto SA, Coleska A, Ran X, Yi H, Yang C.-Y, Wang S. J. Med. Chem. 2012; 55: 1137
  • 10 Jo H, Meinhardt N, Wu Y, Kulkarni S, Hu X, Low KE, Davies PL, DeGrado WF, Greenbaum DC. J. Am. Chem. Soc. 2012; 134: 17704
  • 11 Lau YH, de Andrade P, Quah S.-T, Rossmann M, Laraia L, Skold N, Sum TJ, Rowling PJ. E, Joseph TL, Verma C, Hyvonen M, Itzhaki LS, Venkitaraman AR, Brown CJ, Lane DP, Spring DR. Chem. Sci. 2014; 5: 1804
  • 12 Azzarito V, Long K, Murphy NS, Wilson AJ. Nat. Chem. 2013; 5: 161
  • 13 Lau YH, de Andrade P, Wu Y, Spring DR. Chem. Soc. Rev. 2015; 44: 91
  • 14 Bracken C, Gulyás J, Taylor JW, Baum J. J. Am. Chem. Soc. 1994; 116: 6431
  • 15 Phelan JC, Skelton NJ, Braisted AC, McDowell RS. J. Am. Chem. Soc. 1997; 119: 455
  • 16 Jackson DY, King DS, Chmielewski J, Singh S, Schultz PG. J. Am. Chem. Soc. 1991; 113: 9391
  • 17 Blackwell HE, Grubbs RH. Angew. Chem. Int. Ed. 1998; 37: 3281
  • 18 Schafmeister CE, Po J, Verdine GL. J. Am. Chem. Soc. 2000; 122: 5891
  • 19 Hamachi I, Yamada Y, Matsugi T, Shinkai S. Chem. Eur. J. 1999; 5: 1503
  • 20 Rossi P, Felluga F, Tecilla P, Formaggio F, Crisma M, Toniolo C, Scrimin P. J. Am. Chem. Soc. 1999; 121: 6948
  • 21 Kelso MJ, Hoang HN, Appleton TG, Fairlie DP. J. Am. Chem. Soc. 2000; 122: 10488
  • 22 Cline DJ, Thorpe C, Schneider JP. J. Am. Chem. Soc. 2003; 125: 2923
  • 23 Kubota R, Liu S, Shigemitsu H, Nakamura K, Tanaka W, Ikeda M, Hamachi I. Bioconjugate Chem. 2018; 29: 2058
  • 24 Ojida A, Inoue M, Mito-oka Y, Hamachi I. J. Am. Chem. Soc. 2003; 125: 10184
  • 25 Smith SJ, Du K, Radford RJ, Tezcan FA. Chem. Sci. 2013; 4: 3740
  • 26 Ghadiri MR, Choi C. J. Am. Chem. Soc. 1990; 112: 1630
  • 27 Ruan F, Chen Y, Hopkins PB. J. Am. Chem. Soc. 1990; 112: 9403
  • 28 Signarvic RS, DeGrado WF. J. Am. Chem. Soc. 2009; 131: 3377
  • 29 Hristova YR, Kemper B, Besenius P. Tetrahedron 2013; 69: 10525
  • 30 Yao L.-Y, Hau FK.-W, Yam VW.-W. J. Am. Chem. Soc. 2014; 136: 10801
  • 31 Enomoto M, Kishimura A, Aida T. J. Am. Chem. Soc. 2001; 123: 5608
  • 32 Scherbaum F, Grohmann A, Huber B, Krüger C, Schmidbaur H. Angew. Chem. Int. Ed. 1988; 27: 1544
  • 33 Schmidbaur H, Schier A. Chem. Soc. Rev. 2012; 41: 370
  • 34 Zheng Q, Borsley S, Nichol GS, Duarte F, Cockroft SL. Angew. Chem. Int. Ed. 2019; 58: 12617
  • 35 Kemper B, Zengerling L, Spitzer D, Otter R, Bauer T, Besenius P. J. Am. Chem. Soc. 2018; 140: 534
  • 36 Smith SJ, Radford RJ, Subramanian RH, Barnett BR, Figueroa JS, Tezcan FA. Chem. Sci. 2016; 7: 5453
  • 37 Learte-Aymamí S, Curado N, Rodríguez J, Vázquez ME, Mascareñas JL. J. Am. Chem. Soc. 2017; 139: 16188
  • 38 Kemper B, von Gröning M, Lewe V, Spitzer D, Otremba T, Stergiou N, Schollmeyer D, Schmitt E, Ravoo BJ, Besenius P. Chem. Eur. J. 2017; 23: 6048
  • 39 Lewe V, Preuss M, Woźnica EA, Spitzer D, Otter R, Besenius P. Chem. Commun. 2018; 54: 9498
  • 40 Meier-Menches SM, Casini A. Bioconjugate Chem. 2020; 31: 1279
  • 41 Dogan J, Schulte JB, Swiegers GF, Wild SB. J. Org. Chem. 2000; 65: 951 ; corrigendum: J. Org. Chem. 2000, 65, 4782
  • 42 Bockrath B, Dorfman LM. J. Phys. Chem. 1975; 79: 1509
  • 43 Rohlík Z, Holzhauser P, Kotek J, Rudovský J, Němec I, Hermann P, Lukeš I. J. Organomet. Chem. 2006; 691: 2409
  • 44 Tsvetkov EN, Bondarenko NA, Malakhova IG, Kabachnik MI. Synthesis 1986; 198
  • 45 Schäfer S, Frey W, Hashmi AS. K, Cmrecki V, Luquin A, Laguna M. Polyhedron 2010; 29: 1925
  • 46 Fujimoto Y, Konishi Y, Kubo O, Hasegawa M, Inohara N, Fukase K. Tetrahedron Lett. 2009; 50: 3631
  • 47 Greene TW, Wuts PG. M. Protective Groups in Organic Synthesis, 2nd ed. Wiley; New York: 1991
  • 48 Fmoc-Lys({AuCl[PPh2(CH2)2CO2H]})OH (7) In a Schlenk flask, Au complex 6 (1300 mg, 1.4 mmol, 1.0 equiv) was dissolved in anhyd DCM (5 mL), and the solution was cooled with dry ice to –78 °C. A 1 M solution of BBr3 in DCM (7 mL, 7.0 mmol, 5.0 equiv) was added dropwise, and the slightly orange solution was stirred for 1 h at –78 °C then for 2 h at 0 °C and for 1 h at rt. H2O (20 mL) was added, and the solution was stirred for 10 min. Addition of brine (10 mL) caused a separation of the phases. The aqueous phase was extracted with DCM (3 × 20 mL), and the combined organic phases were dried (Na2SO4). The solvent was removed under reduced pressure, and the crude product was purified by flash chromatography [silica gel, CHCl3–MeOH (99:1) + 0.05 vol% HCO2H] to give a colorless solid; yield: 865 mg (73%, 1.0 mmol); Rf = 0.63 (DCM–MeOH, 99:1 + 0.05 vol% HCO2H). 1H NMR (400 MHz, DMSO-d 6): δ = 12.54 (s, 1 H, COOH), 7.97 (t, J = 5.2 Hz, 1 H, CONHCH2), 7.89 (d, J = 7.5 Hz, 2 H, CH Fmoc), 7.80–7.71 (m, 6 H, CH Fmoc, CHo -Ph), 7.62–7.53 (m, 7 H, CONHCHα, CHm -Ph + p-Ph), 7.42 (t, J = 7.4 Hz, 2 H, CH Fmoc), 7.32 (t, J = 8.0 Hz, 2 H, CH Fmoc), 4.28–4.15 (m, 3 H, CH 2CH Fmoc), 3.92–3.87 (m, 1 H, CH α), 3.01–2.92 (m, 4 H, CH 2NHCOCH 2), 2.36–2.28 (m, 2 H, CH 2P), 1.73–1.53 (m, 2 H, CH 2CH2NHCO), 1.43–1.21 (m, 4 H, CH 2CH 2CH2CH2NHCO). 31P NMR (162 MHz, DMSO-d 6): δ = 32.6. ESI-MS (MeOH): m/z [M + Na]+ calcd for C36H37AuClN2NaO5P: 863.17; found: 836.24; [2M + Na]+ calcd for C72H74Au2Cl2N4NaO10P2: 1705.17; found: 1705.39.
  • 49 Demizu Y, Okitsu K, Yamashita H, Doi M, Misawa T, Oba M, Tanaka M, Kurihara M. Eur. J. Org. Chem. 2016; 2815
  • 50 Pawlowski J, Juhaniewicz J, Tymecka D, Sek S. Langmuir 2012; 28: 17287
  • 51 Chakrabartty A, Kortemme T, Baldwin RL. Protein Sci. 1994; 3: 843
  • 52 Luo P, Baldwin RL. Biochemistry 1997; 36: 8413
  • 53 Hong D.-P, Hoshino M, Kuboi R, Goto Y. J. Am. Chem. Soc. 1999; 121: 8427
  • 54 Greenfield NJ. Nat. Protoc. 2006; 1: 2876
  • 55 Hirota N, Goto Y, Mizuno K. Protein Sci. 2008; 6: 416