Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation

Hui Wang; Lin-Lin Xu; Lin-Qi Shi; Ru-Jiang Ma

doi:10.1007/s10118-024-3169-6

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Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation

RESEARCH ARTICLE | Updated：2024-11-04

- Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation
- Chinese Journal of Polymer Science Vol. 42, Issue 11, Pages: 1710-1718(2024)
- Affiliations：
  
  a.Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China
  b.Haihe Laboratory of Sustainable Chemical Transformations, Tianjin 300192, China
- Author bio：
  
  shilinqi@nankai.edu.cn (L.Q.S.)
  marujiang@nankai.edu.cn (R.J.M.)
- Funds：
- DOI：10.1007/s10118-024-3169-6
  CLC：
- Received：23 April 2024，
  
  Revised：2024-05-18，
  
  Accepted：21 May 2024，
  
  Online First：20 August 2024，
  
  Published：30 November 2024
- Accepted：
Scan QR Code
Wang, H.; Xu, L. L.; Shi, L. Q.; Ma, R. J. Nanochaperones based on hydrophobic interaction and coordination inhibit protein misfolding and fibrillation. Chinese J. Polym. Sci. 2024, 42, 1710–1718

Hui Wang, Lin-Lin Xu, Lin-Qi Shi, et al. Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation[J]. Chinese Journal of Polymer Science, 2024, 42(11): 1710-1718.
Wang, H.; Xu, L. L.; Shi, L. Q.; Ma, R. J. Nanochaperones based on hydrophobic interaction and coordination inhibit protein misfolding and fibrillation. Chinese J. Polym. Sci. 2024, 42, 1710–1718 DOI： 10.1007/s10118-024-3169-6.

Hui Wang, Lin-Lin Xu, Lin-Qi Shi, et al. Nanochaperones Based on Hydrophobic Interaction and Coordination Inhibit Protein Misfolding and Fibrillation[J]. Chinese Journal of Polymer Science, 2024, 42(11): 1710-1718. DOI： 10.1007/s10118-024-3169-6.

摘要

The researchers developed a nanochaperone called nChap-NA

which effectively trap the amyloid monomer and block its fibrillation site by the hydrophobic interaction of the PNIPAM microdomain and the coordination of NTA(Zn). This study may provide a promising strategy for the prophylactic treatment of amyloidosis.

Abstract

Amyloidosis is characterized by the deposition of fibrillar aggregates

with a specific peptide or protein as the primary component

in affected tissues or organs. Excessive proliferation and deposition of amyloid fibrils can cause organismal dysfun

ction and lethal pathological outcomes associated with amyloidosis. In this study

a nanochaperone (nChap-NA) was developed to inhibit protein misfolding and fibrillation by simulating the function of natural molecular chaperones. The nanochaperone was prepared by self-assembly of two block copolymers PEG-

-PCL and PCL-

-P(NIPAM-

-AANTA)

which had a phase-separated surface consisting of hydrophobic PNIPAM microdomains with coordinative NTA(Zn) moieties and hydrophilic PEG chains. The hydrophobic interaction of the PNIPAM microdomain and the coordination of NTA(Zn) synergistically work together to effectively trap the amyloid monomer and block its fibrillation site. Insulin and human islet amyloid polypeptide (hIAPP) were used as model proteins to investigate the nanochaperone's inhibition of amyloid misfolding and fibrillation. It was proved that the nanochaperone could stabilize the natural conformation of the trapped insulin and hIAPP

and effectively inhibit their fibrillation.

In vivo

study demonstrated that the nanochaperone could effectively preserve the bioactivity of insulin and reduce the cytotoxicity caused by hIAPP aggregation. This study may provide a promising strategy for the prophylactic treatment of amyloidosis.

关键词

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