Protein glycation is a non-enzymatic reaction between reducing sugars and amino groups that occurs in vivo and has been implicated in a number of disease states and pathologies including Alzheimer's and diabetes. Although glycation is thought to alter protein structure and function, there is currently little information on the structural consequences of this modification. We have used a model alpha-helix and a model beta-hairpin peptide, and NMR analysis, to investigate the effects of glycation upon secondary structure. Glycation of the dilysine motif within the alpha-helix peptide occurred preferentially at one lysine residue and resulted in severe disruption to the local secondary structure. The area immediately around the site of modification was extremely flexible and the peptide did not adopt a preferred conformation in this area of the helix in 30% TFE. Significant glycation of the beta-hairpin peptide was not detected and the structure was unchanged. These results show that glycation results in local secondary structure distortion of alpha-helices and that preferential glycation occurs in a sequence specific manner. The findings will allow us to interrogate the local environment in other peptides/proteins to predict the likelihood of glycation, and to model the potential effects such modification might have upon structure/function
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