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Effects of N‐terminal modifications on the stability of antimicrobial peptide SAMP‐A4 analogues against protease degradation
Author(s) -
Li Ruifang,
He Songlin,
Yin Kedong,
Zhang Beibei,
Yi Yanjie,
Zhang Meng,
Pei Nanqi,
Huang Liang
Publication year - 2021
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3352
Subject(s) - peptide , antimicrobial , glycosylation , biochemistry , pegylation , protease , hexanoic acid , chemistry , fatty acid , enzyme , organic chemistry , polyethylene glycol
Infections with multidrug‐resistant (MDR) pathogens are increasingly concerning for public health. Synthesized antimicrobial peptide A4 (SAMP‐A4), a peptide computationally designed by our research team, is a potential drug candidate. However, the antimicrobial peptide SAMP‐A4 is easily degraded in serum. To obtain SAMP‐A4 analogues with high biostability, chemical modifications at its N‐terminus, including fatty acid conjugation, glycosylation and PEGylation, were carried out. The results showed that the introduction of hydrophobic fatty acids at the N‐terminus of SAMP‐A4 is better than hydrophilic glycosylation and PEGylation. With increasing fatty acid chain length, the stability of SAMP‐A4 analogues in serum and trypsin solutions is significantly improved, and the activities against MDR bacteria and Candida are significantly enhanced. There is no obvious change in haemolysis even when hexanoic acid is coupled with SAMP‐A4, so the resulting analogue SAMP‐A4‐C6, SAMP‐A4 conjugated with hexanoic acid, is the most likely of the analogues to become a drug.