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微生物基因组学时代的新型遗传技术与方法:新型抗菌药物靶点的鉴定和/或验证

Novel genetic techniques and approaches in the microbial genomics era: identification and/or validation of targets for the discovery of new antibacterial agents.

作者信息

Pucci Michael J

机构信息

Achillion Pharmaceuticals Inc, New Haven, CT 06511, USA.

出版信息

Drugs R D. 2007;8(4):201-12. doi: 10.2165/00126839-200708040-00001.

Abstract

The availability of microbial genome sequences has ushered in the genomics era and has led to numerous technical advancements over the past decade. These advances have been both in the bioinformatics field that has integrated computer-based approaches with biology and in research methods in the laboratory. The advances have assisted scientists in their study of bacterial gene complements and the roles of their gene products in the bacterial life cycle. Assignment of genes as essential to the bacterial cell nominated them as potential targets for antibacterial drugs and spurred attempts to exploit this information and convert it into drugs. At present, these efforts have met with minimal success. There are several possible reasons for these disappointing results including choice of targets and screen designs, compound libraries chosen for screens, and decreased commitment to antibacterial drug discovery by many large pharmaceutical companies. Structure-based approaches could become very effective in the future as methodologies continue to improve.

摘要

微生物基因组序列的可得性开启了基因组学时代,并在过去十年带来了众多技术进步。这些进步既体现在将基于计算机的方法与生物学相结合的生物信息学领域,也体现在实验室研究方法中。这些进展帮助科学家研究细菌的基因组成及其基因产物在细菌生命周期中的作用。将基因认定为对细菌细胞至关重要,这使它们成为抗菌药物的潜在靶点,并促使人们尝试利用这些信息并将其转化为药物。目前,这些努力取得的成功微乎其微。这些令人失望的结果有几个可能的原因,包括靶点和筛选设计的选择、用于筛选的化合物库,以及许多大型制药公司对抗菌药物研发的投入减少。随着方法不断改进,基于结构的方法未来可能会变得非常有效。

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