Human β-Defensin 2 and β-Defensin 3 Chimeric Peptides Reveal the Structural Basis of the Pathogen Specificity of Their Parent Molecules
Human β-Defensin 2 and β-Defensin 3 Chimeric Peptides Reveal the Structural Basis of the Pathogen Specificity of Their Parent Molecules
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DOI：
10.1128/aac.00872-10
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发表时间：
2011-03-01
影响因子：
4.9
通讯作者：
Groetzinger, Joachim
中科院分区：
文献类型：
--
作者：
Jung, Sascha;Mysliwy, Justyna;Groetzinger, Joachim
尽管具有部分序列同一性和结构相似性，人 β-防御素 3 (HBD3) 杀死金黄色葡萄球菌的效率比人 β-防御素 2 (HBD2) 高 4 至 8 倍，而针对大肠杆菌的活性相同。 HBD2/HBD3 嵌合肽的设计和表征表明，不同的分子区域导致其不同的杀伤特性。其中两种嵌合体能够杀死大肠杆菌和金黄色葡萄球菌，其功效甚至比野生型分子更高。此外，这两种嵌合体之一在生理盐浓度存在下仍保持其高杀伤活性。由于它们对许多人类多重耐药病原体具有广谱抗菌活性，这两种人类来源的设计肽代表了新型抗生素的有希望的模板。
Despite partial sequence identity and structural similarity, human beta-defensin 3 (HBD3) kills Staphylococcus aureus with a 4- to 8-fold higher efficiency than human beta-defensin 2 (HBD2), whereas the activities against Escherichia coli are identical. The design and characterization of HBD2/HBD3 chimeric peptides revealed that distinct molecular regions are responsible for their divergent killing properties. Two of the chimeras killed both E. coli and S. aureus with an even higher efficacy than the wild-type molecules. Moreover, one of these two chimeras maintained its high killing activities in the presence of physiologic salt concentrations. Due to the broad spectrum of their antimicrobial activities against many human multidrug-resistant pathogens, these two designer peptides of human origin represent promising templates for a new class of antibiotics.