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Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin B.
Antimicrobial Agents and Chemotherapy ( IF 4.9 ) Pub Date : 2020-09-21 , DOI: 10.1128/aac.00842-20
Kenya E Fernandes 1 , Richard J Payne 2 , Dee A Carter 3
Affiliation  

Lactoferrin (LF) is an iron-binding glycoprotein with broad-spectrum antimicrobial activity. Previously, we discovered that LF synergistically enhanced the antifungal efficacy of amphotericin B (AMB) across a variety of yeast species and subsequently hypothesized that this synergy was enhanced by the presence of small peptides derived from the whole LF molecule. In this study, LF was digested with pepsin under a range of conditions. The resulting hydrolysates exhibited enhanced synergy with AMB compared to its synergy with undigested LF. Samples were analyzed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, and 14 peptides were identified. The sequences of these peptides were predicted by matching their molecular weights to those of a virtual digest with pepsin. The relative intensities of predicted peptides in each hydrolysate were compared with the activity of the hydrolysate, and the structural and physicochemical properties of the peptides were assessed. From this, a 30-residue peptide was selected for synthesis and dubbed lactofungin (LFG). Pure LFG was highly synergistic with AMB, outperforming native LF in all fungal species tested. With potential for further structural and chemical improvements, LFG is an excellent lead for development as an antifungal adjuvant.

中文翻译:

乳铁蛋白衍生的肽乳铁蛋白与两性霉素B强效协同作用。

乳铁蛋白(LF)是一种铁结合糖蛋白,具有广谱抗菌活性。以前,我们发现LF协同增强了两性霉素B(AMB)在多种酵母菌种中的抗真菌功效,随后假设该协同作用因存在于整个LF分子中的小肽而增强。在这项研究中,LF在一定条件下用胃蛋白酶消化。相比于其与未消化的LF的协同作用,所得水解产物显示出与AMB的协同作用增强。使用基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱分析样品,并鉴定了14种肽。这些肽的序列是通过将其分子量与带有胃蛋白酶的虚拟消化物的分子量进行匹配来预测的。将每种水解物中预测的肽的相对强度与水解物的活性进行比较,并评估了肽的结构和理化性质。由此,选择了具有30个残基的肽进行合成并称为乳铁蛋白(LFG)。纯LFG与AMB高度协同,在所有测试的真菌物种中均优于天然LF。LFG具有进一步的结构和化学改进的潜力,是开发抗真菌佐剂的极好线索。在所有测试的真菌物种中均优于天然LF。LFG具有进一步的结构和化学改进的潜力,是开发抗真菌佐剂的极好线索。在所有测试的真菌物种中均优于天然LF。LFG具有进一步的结构和化学改进的潜力,是开发抗真菌佐剂的极好线索。
更新日期:2020-09-21
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