Effects of hydrophobicity on the antifungal activity of alpha-helical antimicrobial peptides.
Effects of hydrophobicity on the antifungal activity of alpha-helical antimicrobial peptides.
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DOI：
10.1111/j.1747-0285.2008.00728.x
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发表时间：
2008-12
影响因子：
3
通讯作者：
Hodges RS
中科院分区：
文献类型：
--
作者：
Jiang Z;Kullberg BJ;van der Lee H;Vasil AI;Hale JD;Mant CT;Hancock RE;Vasil ML;Netea MG;Hodges RS
我们利用D-V13 K（26个残基的两亲性α-螺旋抗菌肽，表示为D1）的一系列类似物来比较和对比疏水性对抗真菌和抗细菌活性的作用与先前用铜绿假单胞菌菌株获得的结果。对接合菌门真菌的抗真菌活性随着疏水性的增加而降低（D-V13 K/A12 L/A20 L/A23 L，表示为D4，最疏水的类似物比D1，最不疏水的类似物活性低6倍）。相反，子囊菌门真菌的抗真菌活性随着疏水性的增加而增加（D4，最疏水的类似物比D1活性高5倍）。溶血活性受到疏水性增加的显著影响，肽D4的溶血性是肽D1的286倍。与肽D4相比，肽D1对接合菌门真菌和子囊菌门真菌的治疗指数分别为1569倍和62倍。为了降低肽D4的溶血活性并提高/保持D4的抗真菌活性，我们在非极性面中心（V16 K）替换另一个赖氨酸残基，产生D5（D-V13 K/V16 K/A12 L/A20 L/A23 L）。与D4相比，这种类似物D5将溶血活性降低了13倍，将对接合菌门真菌的抗真菌活性提高了16倍，并将治疗指数提高了201倍，并且代表了一种独特的方法来控制特异性，同时在D5的非极性面上的两个疏水片段中保持高疏水性。
We utilized a series of analogs of D-V13K (a 26-residue amphipathic α-helical antimicrobial peptide, denoted D1) to compare and contrast the role of hydrophobicity on antifungal and antibacterial activity to the results obtained previously with Pseudomonas aeruginosa strains. Antifungal activity for Zygomycota fungi decreased with increasing hydrophobicity (D-V13K/A12L/A20L/A23L, denoted D4, the most hydrophobic analog was 6-fold less active than D1, the least hydrophobic analog). In contrast, antifungal activity for Ascomycota fungi increased with increasing hydrophobicity (D4, the most hydrophobic analog was 5-fold more active than D1). Hemolytic activity is dramatically affected by increasing hydrophobicity with peptide D4 being 286-fold more hemolytic than peptide D1. The therapeutic index for peptide D1 is 1569-fold and 62-fold better for Zygomycota fungi and Ascomycota fungi, respectively, compared to peptide D4. To reduce the hemolytic activity of peptide D4 and improve/maintain the antifungal activity of D4, we substituted another lysine residue in the center of the nonpolar face (V16K) to generate D5 (D-V13K/V16K/A12L/A20L/A23L). This analog D5 decreased hemolytic activity by 13-fold, enhanced antifungal activity to Zygomycota fungi by 16-fold and improved the therapeutic index by 201-fold compared to D4 and represents a unique approach to control specificity while maintaining high hydrophobicity in the two hydrophobic segments on the nonpolar face of D5.
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影响因子：
4.8
作者：
Kondejewski, LH;Jelokhani-Niaraki, M;Hodges, RS
通讯作者：
Hodges, RS
影响因子：
4.8
作者：
Chen, YX;Mant, CT;Hodges, RS
通讯作者：
Hodges, RS
影响因子：
3.3
作者：
DRENTH, JPH;VANUUM, SHM;VANDERMEER, JWM
通讯作者：
VANDERMEER, JWM
影响因子：
4.1
作者：
Chen, Yuxin;Mant, Colin T.;Hodges, Robert S.
通讯作者：
Hodges, Robert S.
影响因子：
2.9
作者：
Kovacs, JM;Mant, CT;Hodges, RS
通讯作者：
Hodges, RS