Computational and experimental studies on positive ions derived from peptides

蛋白质组学在很大程度上依赖于质谱学来确定至少一小段蛋白质中的氨基酸序列。通常情况下，蛋白质被一种酶(胰酶)分解，一些产物多肽中的氨基酸残基的序列是由它们在质谱学中的碎裂来确定的。多肽碎片的机制仍然不是很清楚。我们正在用几种方法解决这个问题。我们正在研究质子化多肽(通常的靶标)碎片的机制的细节；这经常需要研究更简单的多肽组成单元，即氨基酸。我们还将碎裂研究扩展到两类不同的离子，(1)通过破坏铜离子/肽复合体而在电喷雾质谱仪中形成的多肽的自由基阳离子，以及(2)连接到更高电荷离子(如La3+离子)的多肽的络合物。这两类离子将提供关于多肽的不同类型的信息，并将有助于澄清从受保护的多肽研究中获得的测序信息中的模糊之处。在所有这些实验工作中，将使用密度泛函理论计算来确定中间体的结构并确定它们相互转化的障碍。有机合成中最重要(也是最困难的)反应之一是在两个饱和碳原子之间形成碳-碳单键。最近在约克发现了一种催化各种碳-碳偶联反应的有机金属化合物。我们正在使用计算化学来了解为什么这种催化剂如此高效，并将利用我们的发现来帮助我们设计更好的催化剂。

Proteomics relies very heavily on mass spectrometry to determine the sequence of amino acids in at least a short segment of a protein.  Usually the protein is broken down by an enzyme (trypsin) and the sequences of the amino acid residues in some of the product peptides are determined by their fragmentation in a mass spectrometry.  The mechanisms by which peptides fragment are still not very well understood.  We are addressing this problem in several ways.  We are examining details of the mechanisms by which protonated peptides (the usual target) fragment; this frequently necessitates looking at the even simpler building blocks of peptides, the amino acids.  We are also expanding fragmentation studies into two different classes of ions, (1) radical cations of peptides formed in electrospray mass spectrometry by breaking copper ion / peptide complexes, and (2) complexes of peptides attached to more highly charged ions like a La3+ ion.  These two classes of ions will give different types of information about the peptides and will help clear up ambiguities in the sequencing information obtained from the protnated peptide studies. Throughout all this experimental work Density Functional Theory calculations will be used to determine the structures of intermediates and to determine the barriers to their interconversion.One of the most important (and difficult) reactions in organic synthesis is forming a carbon-carbon single bond between two saturated carbon atoms.  An organometalic compound that catalyzes a wide variety of carbon-carbon coupling reactions has recently been discovered here at York.  We are using computational chemistry to understand why this catalyst is so efficient and will use our findings to help us design even better catalysts.