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【drug-news】杀灭抗性菌的新型药物
Total synthesis successful: Platensimycin, a new antibiotic
Although a number of new antibiotics have been discovered in recent decades, our armory against infection is continually being depleted, as our microscopically small enemies are crafty warriors that develop resistance to current antibiotics. Multiresistant bacteria are a big problem, especially in hospitals. Already weakened patients are easy victims, for which an infection that cannot be treated with antibiotics can quickly become life-threatening. What is needed are active agents that act on completely different sites in the physiological sequence of pathogens than current medicaments. Platensimycin, recently isolated from the mushroom Streptomyces platensis, is such an agent. A Californian team of researchers is now the first to synthesize this natural product completely in the laboratory—a crucial step on the way to a new class of antibiotics.
Platensimycin inhibits an important step of bacterial fatty acid biosynthesis and in this way paralyzes a broad spectrum of Gram-positive bacterial strains. Thus, this natural product in able to kill dangerous germs that have developed resistance not only to established antibiotics but also to standby products. Examples of these include various resistant strains of Staphylococcus aureus and Enterococcus faecium.
To isolate a complex natural product in sufficient quantity and purity for further experiments is usually a difficult and time-consuming, if not impossible, task. Chemists thus follow a different path: They reproduce the natural product in the laboratory from the ground up. This approach is known as total synthesis. To devise such a total synthesis is an enormous scientific challenge. A way must be found to assemble a complicated synthetic molecule faultlessly from simple, available components—and in sufficiently high yield in each reaction step. The total synthesis of platensimycin has now been accomplished by a team headed by the renowned natural products chemist K. C. Nicolaou (The Scripps Research Institute, La Jolla, and University of California, San Diego). Platensimycin consists of an unusual aromatic ring coupled through an amide group to a compact cage structure. The team built these two components—each a veritable challenge for synthetic chemists—separately and then joined them in the final step of the synthesis. "The described chemistry," says Nicolaou, "sets the stage for the synthesis of designed analogues for structure–activity relationship studies in the search for new antibacterial agents." 我来翻译 成功全合成Platensimycin（平板霉素）—-一种新的抗生素
虽然最近几十年大量新的抗生素不断问世，但由于细菌产对目前的抗生素产生了耐药性，我们对于控制感染的能力在持续减弱。多重耐药菌给我们带来了巨大的挑战，特别是在医院。对于体弱者，不能控制的感染很快带来生命威胁。我们需要完全不同于当前药物作用于病原体生理序列位点的药物。Platensimycin从平板链球菌中分离而来，与当前药物具有完全不同的作用机制。现在，加利福利亚的一个研究小组在实验室首次完全合成了这种自然产物—这是进行新一代抗生素生产的关键步骤。
Platensimycin通过阻断细菌脂肪酸生物合成抑制广谱的革兰阳性菌生长。因而该自然产物能杀死对已用和备用抗生素都产生耐药性的病菌，例如各种耐药的金黄色葡萄球菌和***肠球菌株。
为了进一步实验大量分离和纯化自然产物是一件既困难又耗时的工作。化学家采取不同的途径在实验室再生产这种自然产物，这种生产方式称之为全合成。设计一种全合成方法是一种巨大的科学挑战。必须找到一种从简单、可以利用的化学物无误的合成复杂的人工分子的方法，该方法的任何一步必须高产。享有盛誉的自然产物化学家K. C. Nicolaou (The Scripps Research Institute, La Jolla, and University of California, San Diego)领导的研究小组已经完成了全合成platensimycin的任务。Platensimycin由一个罕见的芳香环通过酰胺基连接在致密笼形结构上。该研究小组分别构建了这两种组分，然后在最后将其合成。这两种组分的构建对合成化学家而言都是挑战。Nicolaou说，“在寻找新的抗生素上，描述化学为设计合成的类似物的构效关系研究提供了舞台。” 我再提炼下：
成功全合成Platensimycin（平板霉素）—-一种新的抗生素
Platensimycin从平板链球菌中分离而来，与当前药物具有完全不同的作用机制。
Platensimycin通过阻断细菌脂肪酸生物合成抑制广谱的革兰阳性菌生长。因而该自然产物能杀死对已用和备用抗生素都产生耐药性的病菌，例如各种耐药的金黄色葡萄球菌和***肠球菌株。
自然产物化学家K. C. Nicolaou (The Scripps Research Institute, La Jolla, and University of California, San Diego)领导的研究小组已经完成了全合成platensimycin的任务。Platensimycin由一个罕见的苯环通过酰胺基连接在致密笼形结构上。该研究小组先分别构建了这两种组分，然后在最后一步将其合成。 修改后稍润色：
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作者:admin@医学,生命科学 2011-09-07 17:14
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