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以钌为中心的btp糖簇作为生物膜形成抑制剂

Ruthenium-centred btp glycoclusters as inhibitors for biofilm formation.

作者信息

O'Reilly Ciaran, Blasco Salvador, Parekh Bina, Collins Helen, Cooke Gordon, Gunnlaugsson Thorfinnur, Byrne Joseph P

机构信息

School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin Ireland.

School of Medicine, University College Dublin Belfield Dublin 4 Ireland.

出版信息

RSC Adv. 2021 May 4;11(27):16318-16325. doi: 10.1039/d0ra05107a. eCollection 2021 Apr 30.

Abstract

Carbohydrate-decorated clusters (glycoclusters) centred on a Ru(ii) ion were synthesised and tested for their activity against biofilm formation. These clusters were designed by conjugating a range of carbohydrate motifs (galactose, glucose, mannose and lactose, as well as galactose with a triethylene glycol spacer) to a btp (2,6-bis(1,2,3-triazol-4-yl)pyridine) scaffold. This scaffold, which possesses a symmetry, is an excellent ligand for d-metal ions, and thus the formation of the Ru(ii)-centred glycoclusters 7 and 8Gal was achieved from 5 and 6Gal; each possessing four deprotected carbohydrates. Glycocluster 8Gal, which has a flexible spacer between the btp and galactose moieties, showed significant inhibition of bacterial biofilm formation. By contrast, glycocluster 7, which lacked the flexible linker, didn't show significant antimicrobial effects and neither does the ligand 6Gal alone. These results are proposed to arise from carbohydrate-lectin interactions with LecA, which are possible for the flexible metal-centred multivalent glycocluster. Metal-centred glycoclusters present a structurally versatile class of antimicrobial agent for , of which this is, to the best of our knowledge, the first example.

摘要

合成了以钌(II)离子为中心的碳水化合物修饰簇(糖簇),并测试了它们对生物膜形成的活性。这些簇是通过将一系列碳水化合物基序(半乳糖、葡萄糖、甘露糖和乳糖,以及带有三甘醇间隔基的半乳糖)与btp(2,6-双(1,2,3-三唑-4-基)吡啶)支架共轭设计而成。这种具有对称性的支架是d-金属离子的优良配体,因此由5和6Gal实现了以钌(II)为中心的糖簇7和8Gal的形成;每个都含有四个脱保护的碳水化合物。在btp和半乳糖部分之间具有柔性间隔基的糖簇8Gal对细菌生物膜形成表现出显著抑制作用。相比之下,缺乏柔性连接基的糖簇7没有显示出显著的抗菌作用,单独的配体6Gal也没有。这些结果被认为是由于碳水化合物与LecA的凝集素相互作用引起的,这种相互作用对于以金属为中心的柔性多价糖簇是可能的。以金属为中心的糖簇是一类结构多样的抗菌剂,据我们所知,这是第一个此类例子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad2b/9030604/45607daf35fa/d0ra05107a-s1.jpg

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