化学
部分
残留物(化学)
细胞毒性
抗菌活性
天然产物
立体化学
丙氨酸
抗菌剂
金黄色葡萄球菌
色氨酸
固相合成
组合化学
生物活性
氨基酸
生物化学
有机化学
细菌
肽
体外
生物
遗传学
作者
Carl Rogel V Inocentes,Lilibeth A. Salvador‐Reyes,Aaron Joseph L. Villaraza
标识
DOI:10.1002/cbdv.202200832
摘要
In this report, we describe the facile synthesis of four microcionamide-inspired peptides where the atypical 2-phenylethylenamine (2-PEA) functional group in the marine natural product, microcionamide A, was replaced with a similarly-aromatic but more easily incorporated tryptophan (Trp) residue. Compounds 1-4 were synthesized using a standard Fmoc-based solid-phase synthesis strategy followed by iodine-mediated on-resin cyclization for disulfide-bridged compounds 1-3. Compound 1 showed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa, with minimum inhibitory concentrations (MICs) of 9.1 μM and 15 μM, respectively. The inactivity of alanine analogs 2-4 against these pathogens suggests that the N-terminal Val, the cyclic scaffold, the contiguous Ile residues, and consequently, the hydrophobicity of compound 1 are essential for antibacterial activity. Compound 1 also favorably exhibited minimal cytotoxicity against normal mammalian cell lines. In summary, we have synthesized an analog of microcionamide A where replacement of the 2-PEA moiety with a Trp residue retained the antibacterial activity and with favorably low cytotoxicity.
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