An Antibacterial Peptide with High Resistance to Trypsin Obtained by Substituting d-Amino Acids for Trypsin Cleavage Sites.
An Antibacterial Peptide with High Resistance to Trypsin Obtained by Substituting d-Amino Acids for Trypsin Cleavage Sites.
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DOI：
10.3390/antibiotics10121465
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发表时间：
2021-11-28
期刊：
影响因子：
--
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Zhao X;Zhang M;Muhammad I;Cui Q;Zhang H;Jia Y;Xu Q;Kong L;Ma H
抗菌肽对蛋白酶的稳定性较差，限制了其临床应用。在这些限制中，胰酶主要存在于消化道，这是口服多肽的不可逾越的障碍。OM19R是一种随机卷曲的多聚脯氨酸阳离子抗菌肽，对一些革兰氏阴性菌有较高的抗菌活性，但对胰酶的稳定性较差。根据OM19R的构效关系，将胰酶裂解部位的所有阳离子氨基酸残基(L-精氨酸和L-赖氨酸)替换为相应的d-氨基酸残基，得到了设计的多肽OM19D，既保持了其抗菌活性，又提高了胰酶的稳定性。经高浓度胰酶处理和长时间(如10 mg/mL，8h)处理后，仍具有较高的抗菌活性(MIC=16~32µg/mL)。此外，OM19D对血清、血浆等环境因素也表现出较高的稳定性。它在二级结构和作用机制上与其母体多肽相似。因此，该策略有利于提高抗菌肽的酶稳定性。
The poor stability of antibacterial peptide to protease limits its clinical application. Among these limitations, trypsin mainly exists in digestive tract, which is an insurmountable obstacle to orally delivered peptides. OM19R is a random curly polyproline cationic antimicrobial peptide, which has high antibacterial activity against some gram-negative bacteria, but its stability against pancreatin is poor. According to the structure-activity relationship of OM19R, all cationic amino acid residues (l-arginine and l-lysine) at the trypsin cleavage sites were replaced with corresponding d-amino acid residues to obtain the designed peptide OM19D, which not only maintained its antibacterial activity but also enhanced the stability of trypsin. Proceeding high concentrations of trypsin and long-time (such as 10 mg/mL, 8 h) treatment, it still had high antibacterial activity (MIC = 16–32 µg/mL). In addition, OM19D also showed high stability to serum, plasma and other environmental factors. It is similar to its parent peptide in secondary structure and mechanism of action. Therefore, this strategy is beneficial to improve the protease stability of antibacterial peptides.
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DOI：
10.3402/ljm.v6i0.5870
发表时间：
2011-05-13
期刊：
The Libyan journal of medicine
影响因子：
--
作者：
Askoura M;Mottawea W;Abujamel T;Taher I
通讯作者：
Taher I
D-氨基酸取代增强抗菌肽polybia-CP的稳定性
影响因子：
3.7
作者：
Jia, Fengjing;Wang, Jiayi;Wang, Rui
通讯作者：
Wang, Rui
具有亚 10 nm 分辨率和超灵敏性的尖端增强红外成像
影响因子：
5.7
作者：
Li, Jian;Jahng, Junghoon;Xia, Xing-Hua
通讯作者：
Xia, Xing-Hua
影响因子：
8.4
作者：
Bartoloni M;Jin X;Marcaida MJ;Banha J;Dibonaventura I;Bongoni S;Bartho K;Gräbner O;Sefkow M;Darbre T;Reymond JL
通讯作者：
Reymond JL
影响因子：
7.3
作者：
Karstad, Rasmus;Isaksen, Geir;Svenson, Johan
通讯作者：
Svenson, Johan