Zhao Can, Fernandez Antonio, Avlonitis Nicolaos, Vande Velde Greetje, Bradley Mark, Read Nick D, Vendrell Marc
Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, University of Manchester , CTF Building, Grafton Street, M13 9NT Manchester, United Kingdom.
MRC/UoE Centre for Inflammation Research, The University of Edinburgh , 47 Little France Crescent, EH9 3FJ Edinburgh, United Kingdom.
ACS Comb Sci. 2016 Nov 14;18(11):689-696. doi: 10.1021/acscombsci.6b00081. Epub 2016 Oct 20.
With the advent of antimicrobial resistance, there is an urgent need for new strategies to treat infectious diseases. Antimicrobial peptides are considered as promising candidates, and therefore there is a need to understand their mechanism of action in order to exploit their therapeutic potential. To this end, fluorescent analogs are powerful tools to analyze their behavior and subcellular localization in cells and in vivo. However, the conjugation of fluorophores to antimicrobial peptides, especially in short sequences, can impair their biological activity, making the selection of the fluorescent label an essential step in these studies. In the present work, we have systematically modified a model antifungal hexapeptide with a collection of fluorophores covering broad physicochemical and spectral properties. The resulting conjugates have been examined in two different fungal species, in terms of their activity and intracellular localization. The biological results confirm the influence of the different fluorescent moieties on the subcellular localization of antimicrobial sequences, and provides an insight on the optimal fluorophores to be used in the preparation of fluorescent peptides for different bioimaging assays.
随着抗菌药物耐药性的出现，迫切需要新的策略来治疗传染病。抗菌肽被认为是有前景的候选物，因此有必要了解它们的作用机制，以便发挥其治疗潜力。为此，荧光类似物是分析其在细胞和体内行为及亚细胞定位的有力工具。然而，荧光团与抗菌肽的缀合，尤其是在短序列中，可能会损害其生物活性，使得荧光标记的选择成为这些研究中的关键步骤。在本研究中，我们用一系列具有广泛物理化学和光谱特性的荧光团系统地修饰了一种模型抗真菌六肽。所得缀合物已在两种不同的真菌物种中进行了活性和细胞内定位方面的检测。生物学结果证实了不同荧光部分对抗菌序列亚细胞定位的影响，并为用于不同生物成像分析的荧光肽制备中最佳荧光团的选择提供了见解。
