Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Am Chem Soc. 2009 Dec 9;131(48):17563-5. doi: 10.1021/ja908777t.
The thiocillins are natural-product antibiotics derived from ribosomally encoded peptides that undergo extensive posttranslational modifications to yield the mature trithiazolylpyridine-containing macrocyclic compound. Poor pharmacokinetic properties have prevented the clinical use of these highly potent antibiotics. Through in vivo manipulation of the gene responsible for production of the thiocillin precursor peptide, we have generated 65 novel thiocillin variants, allowing us to explore structure-activity relationships involved in both precursor peptide maturation and antibiotic activity.
硫霉素是一类天然产物抗生素，来源于核糖体编码的肽，这些肽经过广泛的翻译后修饰，生成成熟的含三噻唑基吡啶的大环化合物。较差的药代动力学特性阻碍了这些高效抗生素的临床应用。通过体内操纵负责硫霉素前体肽产生的基因，我们产生了 65 种新型硫霉素变体，使我们能够探索涉及前体肽成熟和抗生素活性的结构-活性关系。
