Comp Chem Research Developments

Jan 22, 2003
 

Spectroscopic and theoretical characterization of tyrosyl radicals in dipeptides

Redox-active tyrosine residues play a fundamental role in biological electron transfer reactions.  Upon radiation with certain frequencies of light, tyrosine residues can form electronically excited tyrosyl radicals that have been postulated to mediate long-distance electron transfer reactions in enzymes such as prostaglandin H synthase, galactose oxidase, ribonucleotide reductase, and photosystem II.  However, the mechanism whereby environmental factors, through interactions with these redox-active tyrosine residues, provide precise functional control that gives rise to specific biological function are not well understood.

Recent spectroscopic studies pioneered by graduate student Idelisa Ayala and Professor Bridgette Barry, in conjunction with theoretical calculations by graduate student Kevin Range and Professor Darrin M. York have provided new insight into how these residues are controlled.  In the Barry lab, tyrosyl radicals were generated with ultraviolet photolysis of polycrystalline tyrosinate or dipeptides and subsequently analyzed with electron paramagnetic resonance (EPR) and reaction-induced FT-IR spectroscopy.  Comparison of spectra from isotopically labeled tyrosyl radicals provides a detailed spectroscopic "fingerprint" of the molecular and electronic structure.  In order to aid in a detailed interpretation of the experimental spectra, theoretical quantum chemical calculations in the York lab were performed using density-functional theory.  Together, the experimental and theoretical results provide a detailed spectroscopic characterization of the tyrosyl radical in dipeptides.  These results lead to the postulate that a perturbation of the peptide amino group occurs via a conformationally sensitive spin-polarization mechanism that indirectly affects the N-H vibrational stretching mode.

This work, published in the Journal of the American Chemical Society, provides an important first step towards a detailed spectral interpretation for protein-based tyrosyl radicals.