Analysis of protein aggregates by combination of cross-linking reactions and chromatographic separations

Chemical cross-linking provides a method that covalently bridges near-neighbour associations within proteins and protein aggregates. Combined with chromatographic separations and protein-chemical methods, it may be used to localize and to investigate three-dimensional relations as present under natural conditions. This paper reviews the chemistry and application of cross-linking reagents and the development of combination experimental approaches in view of chromatographic separations and cross-linking reactions. Investigations of homooligomeric and heterooligomeric protein associations as well as conformational analysis are presented.