High‐Throughput Screening of pH‐Dependent β‐sheet Self‐Assembling Peptide

Author:

Ye Xin‐Wei123,Tian Wen1,Han Lu1,Li Yi‐Jing1,Liu Shan1,Lai Wen‐Jia4,Liu Yi‐Xuan1,Wang Lei1,Yang Pei‐Pei1,Wang Hao1235ORCID

Affiliation:

1. CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun Beijing 100190 China

2. China Sino‐Danish College Sino‐Danish Center for Education and Research University of Chinese Academy of Sciences Beijing 100049 China

3. University of Chinese Academy of Sciences Beijing 100049 China

4. Division of Nanotechnology Development National Center for Nanoscience and Technology (NCNST) No. 11 Beiyitiao, Zhongguancun Beijing 100190 China

5. Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Institution Beijing 100049 China

Abstract

AbstractpH‐dependent peptide biomaterials hold tremendous potential for cell delivery and tissue engineering. However, identification of responsive self‐assembling sequences with specified secondary structure remains a challenge. In this work, An experimental procedure based on the one‐bead one‐compound (OBOC) combinatorial library is developed to rapidly screen self‐assembling β‐sheet peptides at neutral aqueous solution (pH 7.5) and disassemble at weak acidic condition (pH 6.5). Using the hydrophobic fluorescent molecule thioflavin T (ThT) as a probe, resin beads displaying self‐assembling peptides show fluorescence under pH 7.5 due to the insertion of ThT into the hydrophobic domain, and are further cultured in pH 6.5 solution. The beads with extinguished fluorescence are selected. Three heptapeptides are identified that can self‐assemble into nanofibers or nanoparticles at pH 7.5 and disassemble at pH 6.5. P1 (LVEFRHY) shows a rapid acid response and morphology transformation with pH modulation. Changes in the charges of histidine and hydrophobic phenyl motif of phenylalanine may play important roles in the formation of pH‐responsive β‐sheet nanofiber. This high‐throughput screening method provides an efficient way to identify pH‐dependent β‐sheet self‐assembling peptide and gain insights into structural design of such nanomaterials.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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