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Complexation of an Antimicrobial Peptide by Large‐Sized Macrocycles for Decreasing Hemolysis and Improving Stability
Author(s) -
Chen Junyi,
Meng Qingbin,
Zhang Yadan,
Dong Ming,
Zhao Liang,
Zhang Yahan,
Chen Longming,
Chai Yao,
Meng Zhao,
Wang Chenhong,
Jia Xueshun,
Li Chunju
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202102706
Subject(s) - hemolysis , peptide , antimicrobial , macromolecule , chemistry , combinatorial chemistry , stereochemistry , biochemistry , biology , organic chemistry , immunology
Traditional macrocyclic hosts have finite cavity sizes, generally 5–10 Å, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water‐soluble large‐sized quaterphen[ n ]arenes (WQPns, n =3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants ( K a ) of (4.20±0.23)×10 4 M −1 for PXG/WQP3 and (2.46±0.44)×10 5 M −1 for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host–guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.