Three Ring Posttranslational Circuses: Insertion of Oxazoles, Thiazoles, and Pyridines into Protein-Derived Frameworks

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• 作者：Christopher T. Walsh ; Steven J. Malcolmson ; Travis S. Young
• 刊名：ACS Chemical Biology
• 出版年：2012
• 出版时间：March 16, 2012
• 年：2012
• 卷：7
• 期：3
• 页码：429-442
• 全文大小：763K
• 年卷期：v.7,no.3(March 16, 2012)
• ISSN：1554-8937

文摘

Nitrogen heterocycles are the key functional and structural elements in both RNA and DNA, in half a dozen of the most important coenzymes, and in many synthetic drug scaffolds. On the other hand, only 3 of 20 proteinogenic amino acids have nitrogen heterocycles: proline, histidine, and tryptophan. This inventory can be augmented in microbial proteins by posttranslational modifications downstream of leader peptide regions that convert up to 10 serine, threonine, and cysteine residues, side chains and peptide backbones, into oxazoles, thiazoles, and pyridine rings. Subsequent proteolysis releases these heterocyclic scaffolds in both linear and macrocyclic frameworks as bioactive small molecules.