Department of Infection, Immunity & Inflammation, University of Leicester, Leicester, LE1 9HN, UK.
MIP Diagnostics Ltd, Fielding Johnson Bldg., University of Leicester, Leicester, LE1 7RH, UK.
Angew Chem Int Ed Engl. 2017 Dec 22;56(52):16555-16558. doi: 10.1002/anie.201709313. Epub 2017 Dec 1.
We describe the development, characterization, and biological testing of a new type of linear molecularly imprinted polymer (LMIP) designed to act as an anti-infective by blocking the quorum sensing (QS) mechanism and so abrogating the virulence of the pathogen Streptococcus pneumoniae. The LMIP is prepared (polymerized) in presence of a template molecule, but unlike in traditional molecular imprinting approaches, no cross-linker is used. This results in soluble low-molecular-weight oligomers that can act as a therapeutic agent in vitro and in vivo. The LMIP was characterized by mass spectrometry to determine its monomer composition. Fragments identified were then aligned along the peptide template by computer modeling to predict the possible monomer sequence of the LMIP. These findings provide a proof of principle that LMIPs can be used to block QS, thus setting the stage for the development of LMIPs a novel drug-discovery platform and class of materials to target Gram-positive pathogens.
我们描述了一种新型线性分子印迹聚合物 (LMIP) 的开发、表征和生物学测试，该聚合物旨在通过阻断群体感应 (QS) 机制来发挥抗感染作用，从而削弱病原体肺炎链球菌的毒力。LMIP 是在模板分子存在的情况下制备（聚合）的，但与传统的分子印迹方法不同，不使用交联剂。这导致可溶的低分子量寡聚物，可在体外和体内作为治疗剂发挥作用。通过质谱法对 LMIP 进行了表征，以确定其单体组成。然后通过计算机建模将鉴定出的片段与肽模板对齐，以预测 LMIP 的可能单体序列。这些发现提供了一个原理证明，即 LMIP 可用于阻断 QS，从而为 LMIP 的开发奠定了基础，这是一种新的药物发现平台和一类针对革兰氏阳性病原体的材料。
