Skip to main content
SpringerLink
Log in

Effect of a Short Peptide with Alternating L- and D-Amino Acid on the Aggregation and Membrane Damage of hIAPP

  • Article
  • Published:
Chemical Research in Chinese Universities Aims and scope

Abstract

Alpha-sheet is believed to be a significant structural compo-nent, formed in the fibrillation process of the amyloid pep-tide. However, the knowledge about the role of a-sheet played in the amyloidosis and toxicity is lack. In this work, we modi-fied a short peptide derived from the core region of human islet amyloid polypetide(hIAPP, hIAPP18–27) with an alternating D-amino acid replacement and investigated the effects of the L/D alternating peptide on the fibrillar aggregation and the membrane damage of hIAPP using NMR, ThT fluorescence assay, circular dichroism(CD), transmission electron microscopy(TEM) and leakage assay, and com-pared the results with those of hIAPP18–27 without D-amino acid re-placement. We show that the short peptide with alternating L- and D-amino acids forms an a-sheet structure and is more potent in pro-moting the fibrillation of hIAPP and reducing the ability of hIAPP to disrupt the membrane composed of POPG and POPC[1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine] 1:4 lipids than the short pep-tide with all L-amino acids in a random coil structure. The higher po-tency of the D/L alternating peptide in these activities is attributed to its ability to induce the a-sheet-like structure in the core region of hIAPP and block the interaction of hIAPP with the membrane more effectively.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Soto C. FEBS Lett., 2001, 498, 204

    Article  CAS  Google Scholar 

  2. Chiti F., Dobson C. M., Nat. Chem. Biol., 2009, 5, 15

    Article  CAS  Google Scholar 

  3. Wei G., Su Z., Reynolds N. P., Arosio P., Hamley I. W., Gazit E., Mezzenga R., Chem. Soc. Rev., 2017, 46, 4661

    Article  CAS  Google Scholar 

  4. Butterfield S. M., Lashuel H. A., Angew. Chem., Int. Ed., 2010, 49, 5628

    Article  CAS  Google Scholar 

  5. Serpell L. C., Biochim. Biophys. Acta, 2000, 1502, 16

    Article  CAS  Google Scholar 

  6. Kotler S. A., Walsh P., Brender J. R., Ramamoorthy A., Chem. Soc. Rev., 2014, 43, 6692

    Article  CAS  Google Scholar 

  7. Ke P. C., Sani M. A., Ding F., Kakinen A., Javed I., Separovic F., Davis T. P., Mezzenga R., Chem. Soc. Rev., 2017, 46, 6492

    Article  CAS  Google Scholar 

  8. Daggett V., Acc. Chem. Res., 2006, 39, 594

    Article  CAS  Google Scholar 

  9. Armen R. S., Bernard B. M., Day R., Alonso D. O. V., Daggett V., Proc. Natl. Acad. Sci. USA, 2005, 102, 13433

    Article  CAS  Google Scholar 

  10. Armen R. S., DeMarco M. L., Alonso D. O. V., Daggett V., Proc. Natl. Acad. Sci. USA, 2004, 101, 11622

    Article  CAS  Google Scholar 

  11. Wu H., Canfield A., Adhikari J., Huo S., J. Comput. Chem., 2010, 31, 1216

    Article  CAS  Google Scholar 

  12. Xu S., J. Phys. Chem. B, 2009, 113, 12447

    Article  CAS  Google Scholar 

  13. Hilaire M. R., Ding B., Mukherjee D., Chen J., Gai F., J. Am. Chem. Soc., 2018, 140, 629

    Article  CAS  Google Scholar 

  14. Bleem A., Francisco R., Bryers J. D., Daggett V., Npj Biofilms Microbi., 2017, 3, 16

    Article  Google Scholar 

  15. Pauling L., Corey R. B., Proc. Natl. Acad. Sci. USA, 1951, 37, 251

    Article  CAS  Google Scholar 

  16. Kellock J., Hopping G., Caughey B., Daggett V., J. Mol. Biol., 2016, 428, 2317

    Article  CAS  Google Scholar 

  17. Maris N. L., Shea D., Bleem A., Bryers J. D., Daggett V., Biochemistry, 2018, 57, 507

    Article  CAS  Google Scholar 

  18. Hopping G., Kellock J., Barnwal R. P., Law P., Bryers J., Varani G., Caughey B., Daggett V., Elife, 2014, 3, e01681

    Article  Google Scholar 

  19. Shea D., Hsu C. C., Bi T. M., Paranjapye N., Childers M. C., Cochran J., Tomberlin C. P., Wang L., Paris D., Zonderman J., Varani G., Link C. D., Mullan M., Daggett V., Proc. Natl. Acad. Sci. USA, 2019, 116, 8895

    Article  CAS  Google Scholar 

  20. Fernandez M. S., Cell Calcium., 2014, 56, 416

    Article  CAS  Google Scholar 

  21. Cao P., Marek P., Noor H., FEBS Lett., 2013, 587, 1106

    Article  CAS  Google Scholar 

  22. Abedini A., Schmidt A. M., FEBS Lett., 2013, 587, 1119

    Article  CAS  Google Scholar 

  23. Kiriyama Y., Nochi H., Cells, 2018, 7, 1

    Article  Google Scholar 

  24. Scrocchi L. A., Chen Y., Waschuk S., Wang F., Cheung S., Darabie A. A., McLaurin J., Fraser P. E., J. Mol. Biol., 2002, 318, 697

    Article  CAS  Google Scholar 

  25. Wang S., Meng F., Hao R., Wang C., Li F., Biochim. Biophys. Acta Biomembr., 2020, 1862, 183108

    Article  CAS  Google Scholar 

  26. Meng F., Lu T., Li F., J. Phys. Chem. B, 2019, 123, 9576

    Article  CAS  Google Scholar 

  27. Lu T., Meng F., Wei Y., Li Y., Wang C., Li F., Phys. Chem. Chem. Phys., 2018, 20, 8976

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China(No.21673099).

Author information

Authors and Affiliations

  1. State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, 130012, P. R. China

    Feihong Meng, Yajie Wang, Tong Lu, Chunyu Wang & Fei Li

Authors
  1. Feihong Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yajie Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fei Li.

Ethics declarations

The authors declare no conflicts of interest.

Supporting Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Meng, F., Wang, Y., Lu, T. et al. Effect of a Short Peptide with Alternating L- and D-Amino Acid on the Aggregation and Membrane Damage of hIAPP. Chem. Res. Chin. Univ. 37, 787–794 (2021). https://doi.org/10.1007/s40242-021-0386-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40242-021-0386-1

Keywords

Search

Navigation