Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, United States.
ACS Chem Biol. 2012 Mar 16;7(3):429-42. doi: 10.1021/cb200518n. Epub 2012 Jan 17.
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.
氮杂环是 RNA 和 DNA 的关键功能和结构单元，也是半胱氨酸、色氨酸和苏氨酸 6 种最重要的辅酶以及许多合成药物支架的关键功能和结构单元。另一方面，20 种蛋白质氨基酸中只有 3 种含有氮杂环：脯氨酸、组氨酸和色氨酸。这种成分可以通过前导肽区域下游的翻译后修饰来增加微生物蛋白中的氮杂环，这些修饰可以将多达 10 个丝氨酸、苏氨酸和半胱氨酸残基、侧链和肽骨架转化为噁唑、噻唑和吡啶环。随后的蛋白水解将这些杂环支架释放为线性和大环骨架中的生物活性小分子。
