Grant: Discovery Grants Program - Individual

This project involves fundamental chemistry of peptides. Peptides are small molecules composed of amino acids, the building blocks of proteins. How amino acids are combined defines the structure of a protein and its biological function. We determine the sequence of amino acids using an enzyme to break the protein into peptides. I study the structures of protonated peptides and how they break apart in a mass spectrometer. Amino acid residues are usually lost from one end of a protonated peptide. This makes it possible to identify a peptide (and hence the protein from which it was derived) from the fragments formed. Problems arise when linear intermediate ions rearrange via cyclic ions and then reopen to different linear ions. This leads to incorrect sequence information. In this proposal, I will examine the structures of unusual ions formed in the fragmentation of protonated peptides using a combination of mass spectrometry, molecular modeling and infrared spectroscopy. Theory will provide insights into mechanisms by which these ions fragment and/or rearrange. Peptide radical cations are another class of ions, first discovered by us in 2000, that also provides additional structural information. The plan is to discover whether the reactions of radical cations are charge-induced or radical-induced. We will make a new class of ions, diradical peptides. We will look for evidence of cyclic intermediates when these peptide radical cations break apart. Radicals are of interest because they are important in many diseases and in the process of aging. Peptide radical cations were first made from dipositively charged copper/peptide complexes. This encouraged us to study tripositive lanthanum/peptide complexes and led us to discover a third class of doubly charged organic ions derived from peptides. These are fragile. Recently we have discovered how to stabilize them. The fundamental chemistries of these highly charged ions will be examined.