Department of Electrical and Computer Engineering, UC San Diego, CA, USA.
Proteomics. 2011 Sep;11(18):3642-50. doi: 10.1002/pmic.201000697. Epub 2011 Aug 9.
Some of the most effective antibiotics (e.g. Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of MS-based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage MS, and show its advantages over single-stage MS. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria.
一些最有效的抗生素（例如万古霉素和达托霉素）是由非核糖体生物合成途径产生的环肽。虽然已经对数百种具有生物医学重要性的环肽进行了测序，但环肽测序的计算技术仍处于起步阶段。以前用于测序肽类抗生素和其他环肽的方法基于核磁共振波谱学，并且需要大量（毫克级）的纯化材料，而对于大多数化合物来说，这是不可能获得的。最近，基于 MS 的方法的发展为使用皮克级别的材料对环肽进行准确测序提供了一些希望。在本文中，我们开发了一种通过多级 MS 对环肽进行测序的方法，并展示了其相对于单级 MS 的优势。该方法在芽孢杆菌 Brevis、瞿麦和灰色链霉菌中的已知和新的环肽以及海洋细菌产生的新的环肽家族中进行了测试。
