Antimicrobial activity and stability of the D-amino acid substituted derivatives of antimicrobial peptide polybia-MPI.

Antimicrobial activity and stability of the D-amino acid substituted derivatives of antimicrobial peptide polybia-MPI.
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抗菌肽polybia-MPI D-氨基酸取代衍生物的抗菌活性和稳定性

DOI:
10.1186/s13568-016-0295-8
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发表时间:
2016-12
期刊:
影响因子:
3.7
通讯作者:
Wang R
Wang R
中科院分区:
工程技术3区
文献类型:
--
作者:
Zhao Y;Zhang M;Qiu S;Wang J;Peng J;Zhao P;Zhu R;Wang H;Li Y;Wang K;Yan W;Wang R

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Antimicrobial peptide has the potential to be developed as new kind of antimicrobial agents with novel action mechanism. However, the susceptibility to protease is a drawback for potential peptides to be clinical used. d-amino acid substitution can be one way to increase the proteolytic stability of peptides. In the present study, we synthesized the d-lysines substituted analog (d-lys-MPI) and the d-enantiomer of polybia-MPI (D-MPI) to improve the proteolytic resistance of polybia-MPI. Our results showed that, the stability of its d-amino acid partially substituted analog d-lys-MPI was increased. However, it lost antimicrobial activity at the tested concentration with the loss of α-helix content. As shown in the CD spectra, after substitution, the spectra of D-MPI is symmetrical to MPI, indicated it turned into left hand α-helical conformation. Excitingly, the stability of D-MPI toward the tested protease was improved greatly. Notably, the antimicrobial activity of D-MPI was comparable to its L-counterpart MPI, even improved. In addition, the hemolytic activity of D-MPI was lowered. This also indicated that the action target of antimicrobial peptide polybia-MPI was not chiral specific. So,
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