STRUCTURAL STUDIES OF GRAMICIDIN & OTHER SELF-ASSOCIATING PEPTIDES

Washington University, Saint Louis MO

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goal is to develop mass spectrometry combined with H/D exchange to study peptide and protein association reactions. Therefore, we chose gramicidin as the subject of our method development of MS methods to study the association of peptides and proteins in solution. Gramicidin is a membrane pentadecapeptide that acts as a channel, allowing the passage of monovalent metal ions and assisting in bacterial cell death. The active form is a noncovalently bound dimer. One means to study the self-assembly of this peptide has been to compare the state of the peptide in various solvents ranging from hydrophilic (e.g., trifluoroethanol) to hydrophobic (e.g., n-propanol). We are investigating the use of electrospray mass spectrometry to study the self-assocn. of gramicidin in various org. and mixed solvents that are introduced directly into the mass spectrometer. The dimer (both homo and hetero) can survive the introduction into the gas phase, and the amt. in the gas phase increases with the decreasing dielec. const. of the solvent, reflecting soln.-phase behavior. Tandem mass spectrometry data reveal that the stability of dimer in the gas phase decreases with increasing metal ion size, strongly suggesting that the metal ion binds inside the dimer between the monomers.