奥利万星：作用机理。,Clinical Infectious Diseases

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奥利万星：作用机理。
Clinical Infectious Diseases ( IF 8.2 ) Pub Date : 2012-03-28 , DOI: 10.1093/cid/cir920
George G Zhanel ₁ , Frank Schweizer , James A Karlowsky

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奥利万星是万古霉素的半合成脂糖肽类似物，其中含有所有糖肽共有的七肽核心。它与万古霉素的区别在于二糖糖上存在疏水性N-4-（4-氯苯基）苄基（也称为4'-氯联苯甲基）取代基，在氨基酸上添加了4-表-香豆胺单糖环6中的残基残基被4-表-二十烷胺取代。奥利万星的一种作用机理是通过与革兰氏阳性细菌中的D-丙氨酰-D-丙氨酸干末端结合而抑制转糖基化（在肽聚糖合成中很重要）。通过抑制转糖基化来抑制肽聚糖合成对于所有糖肽（万古霉素）和脂糖肽都是普遍的。奥利万星与肽聚糖中五糖基（Asp / Asn）桥接片段的二级结合也发生了，这使其与万古霉素区别开来，并有助于奥利万星与抗万古霉素的生物体的活性。疏水性4'-氯联苯甲基的存在允许细胞膜相互作用和破坏，从而导致去极化，通透性和浓度依赖性的快速细胞死亡。该机制与特拉万星共有，但万古霉素不共有，并且导致针对达托霉素不敏感的生物体具有活性。总之，奥利万星的作用机制涉及至少三种已知机制：转糖基化抑制，转肽抑制和细胞膜相互作用/破坏。奥利万星'

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Oritavancin: mechanism of action.

Oritavancin is a semisynthetic lipoglycopeptide analogue of vancomycin that contains the heptapeptide core common to all glycopeptides. It differs from vancomycin by the presence of a hydrophobic N-4-(4-chlorophenyl)benzyl (also referred to as 4'-chlorobiphenylmethyl) substituent on the disaccharide sugar, the addition of a 4-epi-vancosamine monosaccharide to the amino acid residue in ring 6, and the replacement of the vancosamine moiety by 4-epi-vancosamine. One mechanism of action of oritavancin is inhibition of transglycosylation (important in peptidoglycan synthesis) by binding to D-alanyl-D-alanine stem termini in Gram-positive bacteria. The inhibition of peptidoglycan synthesis via inhibition of transglycosylation is common to all glycopeptides (vancomycin) and lipoglycopeptides. Secondary binding of oritavancin to the pentaglycyl (Asp/Asn) bridging segment in peptidoglycan also occurs, which distinguishes it from vancomycin and contributes to oritavancin's activity versus vancomycin-resistant organisms. The presence of the hydrophobic 4'-chlorobiphenylmethyl group allows for interaction and disruption of the cell membrane, resulting in depolarization, permeabilization, and concentration-dependent, rapid cell death. This mechanism is shared with telavancin but not vancomycin and results in activity against daptomycin-nonsusceptible organisms. In conclusion, oritavancin's mechanism of action involves at least 3 known mechanisms: inhibition of transglycosylation, inhibition of transpeptidation, and cell membrane interaction/disruption. Oritavancin's multiple mechanisms of action confer activity against vancomycin-susceptible and -resistant organisms, as well as rapid, concentration-dependent killing versus actively growing, stationary phase, and biofilm-producing Gram-positive bacteria.

更新日期：2019-11-01

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