Download PDF
Synlett 2022; 33(07): 669-673
DOI: 10.1055/a-1754-2437
letter

Outside-In Strategy for Peptide-Based Methacrylate and Methacrylamide Zwitterionic Cross-Linkers

Moubani Chakraborty
,
Kristopher V. Waynant∗
University of Idaho Start-Up Funds
› Further Information
    Permissions and Reprints All articles of this category


Abstract

Polyampholyte hydrogels have shown promise as functional biomaterial platforms with resistance to nonspecific protein adsorption (nonbiofouling). Yet there are few zwitterionic cross-linkers available to complement these materials and to provide an extended charge density throughout the 3D network. The recent development of peptide-based zwitterionic cross-linkers has shown merit. Indeed, the use of functionalizable amino acids permits the synthesis of a series of peptide-based zwitterionic methacrylate and methacrylamide cross-linkers. Methacrylate additions prior to peptide coupling provide an outside-in strategy when using natural l-serine or l-lysine as substrates to produce a series of methacrylate and methacrylamide combinations, expanding the library of peptide-based cross-linkers. Here, we describe the preparation of such dipeptide combinations as Ser-Lys, Lys-Ser, and Lys-Lys in zwitterionic bis(methacrylate/methacrylamide) cross-linkers. To highlight the utility of this method and its potential to increase the distance between zwitterionic components, syntheses of the tripeptide Lys-Gly-Lys dimethacrylamide and Ser-Gly-Ser dimethacrylate are reported.

Key words

zwitterions - cross-linkers - peptides - methacrylates - methacrylamides - polyampholytes

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1754-2437.
  • Supporting Information


Publication History

Received: 24 November 2021

Accepted after revision: 28 January 2022

Accepted Manuscript online:
28 January 2022

Article published online:
21 February 2022

© 2022. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

    • 1a Bernards M, He Y. J. Biomater. Sci., Polym. Ed. 2014; 25: 1479
      CrossrefPubMed
    • 1b Zurick KM, Bernards M. J. Appl. Polym. Sci. 2014; 131: 40069
      Crossref
  • 2 Hu W, Wang Z, Xiao Y, Zhang S, Wang J. Biomater. Sci. 2019; 7: 843
    CrossrefPubMed
    • 3a Bergstrand A, Rahmani-Monfared G, Ostlund A, Nydén M, Holmberg K. J. Biomed. Mater. Res., Part A 2009; 88: 608
      CrossrefPubMed
    • 3b Hucknall A, Rangarajan S, Chilkoti A. Adv. Mater. (Weinheim, Ger.) 2009; 21: 2441
      Crossref
    • 3c Ferris R, Hucknall A, Kwon BS, Chen T, Chilkoti A, Zauscher S. Small 2011; 7: 3032
      CrossrefPubMed
    • 3d Fontes CM, Achar RK, Joh DY, Ozer I, Bhattacharjee S, Hucknall A, Chilkoti A. Langmuir 2019; 35: 1379
      CrossrefPubMed
    • 3e Ma H, Hyun J, Stiller P, Chilkoti A. Adv. Mater. (Weinheim, Ger.) 2004; 16: 338
      Crossref
    • 4a Ishida T, Kiwada H. Int. J. Pharm. (Amsterdam, Neth.) 2008; 354: 56
      PubMed
    • 4b Hashimoto Y, Shimizu T, Abu Lila AS, Ishida T, Kiwada H. Biol. Pharm. Bull. 2015; 38: 417
      CrossrefPubMed
    • 4c Lubich C, Allacher P, de la Rosa M, Bauer A, Prenninger T, Horling FM, Siekmann J, Oldenburg J, Scheiflinger F, Reipert BM. Pharm. Res. 2016; 33: 2239
      CrossrefPubMed
    • 5a Jain P, Hung H.-C, Li B, Ma J, Dong D, Lin X, Sinclair A, Zhang P, O’Kelly MB, Niu LQ, Jiang S. Langmuir 2019; 35: 1864
      CrossrefPubMed
    • 5b Carr LR, Xue H, Jiang S. Biomaterials 2011; 32: 961
      CrossrefPubMed
    • 5c Kasák P, Kroneková Z, Krupa I, Lacík I. Polymer 2011; 52: 3011
      Crossref
    • 5d Guo Q, Sun H, Wu X, Yan Z, Tang C, Qin Z, Yao M, Che P, Yao F, Li J. Chem. Mater. 2020; 32: 6347
      Crossref
  • 6 Chakraborty M, Haag SL, Bernards MT, Waynant KV. Biomater. Sci. 2021; 9: 5508
    CrossrefPubMed
    • 7a Liu Q, Li W, Singh A, Cheng G, Liu L. Acta Biomater. 2014; 10: 2956
      CrossrefPubMed
    • 7b Liu Q, Singh A, Liu L. Biomacromolecules 2013; 14: 226
      CrossrefPubMed
    • 7c Zhu J, Liu D, He C. RSC Adv. 2016; 6: 85612
      Crossref
  • 8 Mariner E, Haag SL, Bernards MT. Biointerphases 2019; 14: 3
    CrossrefPubMed
    • 9a Koc J, Schönemann E, Wanka R, Aldred N, Clare AS, Gardner H, Swain GW, Hunsucker K, Laschewsky A, Rosenhahn A. Biofouling 2020; 36: 646
      CrossrefPubMed
    • 9b Laschewsky A, Rosenhahn A. Langmuir 2019; 35: 1056
      CrossrefPubMed
  • 10 Wuts PG. M, Greene TW. Greene’s Protective Groups in Organic Synthesis, 4th ed. Wiley-Interscience; Hoboken: 2006: 533
    CrossrefGoogle Scholar
  • 11 Xu Q, He C, Xiao C, Yu S, Chen X. Polym. Chem. 2015; 6: 1758
    Crossref
  • 12 Twibanire J.-dA. K, Grindley TB. Org. Lett. 2011; 13: 2988
    CrossrefPubMed
  • 13 N-Lys-Gly-Lys Dimethacrylate Trifluoroacetic Acid Salt (8); Typical Procedure The purified globally protected compound 21 (10 mg, 0.16 mmol) was dissolved in 1:2 F3CO2D–CDCl3, and the mixture was stirred at r.t. while the reaction was monitored by NMR. When the reaction was complete, the solvent was removed in vacuo and the product was collected as a colorless oil; yield: 8 mg (86%). FT-IR (thin-film): 2935, 1736, 1655, 1609, 1534, 1176, 1132 cm–1. 1H NMR (500 MHz, CD3OD): δ = 5.70–5.65 (m, 2 H), 5.36 (dq, J = 6.3, 1.5 Hz, 2 H), 4.39 (dd, J = 8.7, 4.9 Hz, 1 H), 3.98 (d, J = 6.8 Hz, 1 H), 3.90–3.85 (m, 2 H), 3.29–3.20 (m, 5 H), 1.93 (d, J = 1.3 Hz, 6 H), 1.91–1.84 (m, 4 H), 1.76–1.70 (m, 2 H), 1.58 (ddd, J = 15.2, 7.6, 3.3 Hz, 4 H), 1.49–1.39 (m, 2 H). 13C NMR (125 MHz, CD3OD): δ = 175.2, 171.4, 171.3, 170.8, 170.6, 162.2 (q, J C–F = 35.11 Hz, C=O), 141.4, 141.3, 130.5 (q, J C–F = 292.75 Hz, CF3), 120.4, 120.2, 54.5, 53.6, 43.0, 40.3, 39.9, 32.3, 32.1, 30.0, 29.9, 24.2, 23.1, 18.8, 18.8. HRMS (ESI/Q-TOF): m/z [M – H]– calcd for C22H37N5O6: 466.2666; found: 466.2673. For other experimental procedures and characterization data, see the Supporting Information.