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新型金纳米簇偶联合成肽:对大肠杆菌 O157:H7 和耐甲氧西林金黄色葡萄球菌(MRSA)的抗生素活性。

New Synthetic Peptides Conjugated to Gold Nanoclusters: Antibiotic Activity Against Escherichia coli O157:H7 and Methicillin-Resistant Staphylococcus aureus (MRSA).

机构信息

Laboratorio de Espectroscopía Atómica y Molecular (LEAM), Centro de Materiales y Nanociencias (CMN), Parque Tecnológico Guatiguará, Universidad Industrial de Santander, Piedecuesta, 681012, Colombia.

Laboratorio de Síntesis de Péptidos, Núcleo de Biotecnología Curauma (NBC), Pontificia Universidad Católica de Valparaíso, 2373223, Valparaíso, Chile.

出版信息

Protein J. 2019 Oct;38(5):506-514. doi: 10.1007/s10930-019-09840-9.

DOI:10.1007/s10930-019-09840-9
PMID:31119600
Abstract

Gold nanoclusters protected with bovine serum albumin (AuNC) can be used in multiple biomedical applications through functionalization with two new and bioactive peptides. Both cationic peptides sequences of 17 amino acids in length and the cysteine residue at its C-terminus were designed and synthesized. Peptides were obtained by solid phase synthesis using the Fmoc strategy. Peptides may be coupled via disulfide bonds to AuNC with hydrodynamic size ~ 2 nm ± 0.3 determined by dynamic light scattering and it had a zeta potential value equal to - 42 mV. Peptides named NBC2253 and NBC2254 were attached to the AuNC using N-succinimidyl-3-(2-pyridyl-dithiol) propionate as crosslinker agent. AuNC@NBC2253 was more active against methicillin-resistant Staphylococcus aureus (MIC50 6.5 µM) and AuNC@NBC2254 exhibited higher antimicrobial activity than the free peptides on Escherichia coli O157:H7 (MIC50 3.5 µM). No hemolysis was detected for any of the peptides. It is evidenced that these antimicrobial peptides conjugated to AuNC serve as promising agents to combat some multi-resistant bacterial strains and that the specific binding of these antimicrobial peptides to gold nanoclusters improves the interaction of these nanostructured systems with the biological target.

摘要

牛血清白蛋白(BSA)保护的金纳米簇(AuNC)可以通过与两种新的生物活性肽进行功能化,应用于多种生物医学领域。这两种阳离子肽序列长度为 17 个氨基酸,C 末端含有半胱氨酸残基,均经过设计和合成。采用 Fmoc 策略通过固相合成获得这些肽。肽可以通过二硫键与 AuNC 偶联,AuNC 的水动力尺寸约为 2nm ± 0.3nm,通过动态光散射法确定,其等电点值为-42mV。使用 N-琥珀酰亚胺基-3-(2-吡啶基二硫代)丙酸作为交联剂,将肽 NBC2253 和 NBC2254 连接到 AuNC 上。AuNC@NBC2253 对耐甲氧西林金黄色葡萄球菌(MIC50 为 6.5μM)的活性更高,而 AuNC@NBC2254 对大肠杆菌 O157:H7 的抗菌活性高于游离肽(MIC50 为 3.5μM)。任何肽都没有检测到溶血现象。这些实验结果表明,与 AuNC 结合的这些抗菌肽可作为对抗某些多耐药菌株的有前途的药物,并且这些抗菌肽与金纳米簇的特异性结合提高了这些纳米结构系统与生物靶标的相互作用。

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