TuO-10


A STUDY OF KYNURENINE FRAGMENTATION MECHANISMS

Santiago Vazquez, Allan Weimann, Roger J. W. Truscott and Margaret M. Sheil

Department of Chemistry, The University of Wollongong, NSW, 2522


The human lens contains a variety of compounds that act as UV filters removing much of the light transmitted by the cornea in the 300 - 400nm region. This function is predominantly performed by the tryptophan metabolites, 3-hydroxykynurenine O-glucoside (3OHKG) and 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O-glucoside (AHBG), while kynurenine (Kyn) and 3-hydroxykynurenine (3OHKyn) are also present to a lesser extent. The function, the mechanisms of production of these compounds and their possible involvement in cataractogenisis are not fully understood and they are the subject of active research.

Although many of these UV filters were identified a number of years ago, AHBG was characterised only recently and at least one other filter remains to be identified [1]. One difficulty with the characterisation of UV filter compounds is that they can often be only isolated in very small amounts thus precluding NMR characterisation. Therefore the potential for an improved understanding of the ESI fragmentation of Kyn (and its derivatives) will ultimately be useful in the structural characterisation of new UV filter compounds.

The work described here involved a detailed study of the fragmentation observed in MS and MS/MS spectra of protonated kynurenine ionised by electrospray. Various techniques were used including: product ion scans, precursor ion scans, high resolution ESI and deuterium exchange combined with product ion scans. This multi-faceted approach demonstrates the usefulness of ESI-MS/MS as a tool for the characterisation of small molecules and has allowed elucidation of the major fragmentation pathways of protonated kynurenines.

1. R. J. W. Truscott, A. M. Wood, J. A. Carver, M. M. Sheil, G. M. Stutchbury, J. Zhu, G. W. Kilby, FEBS Letters 348, 173-176 (1994).