Mass spectrometry to detect the site specificity of advanced glycation/lipoxidation end-product formation on protein: some challenges and solutions.
Formation of AGEs (advanced glycation end-products) and ALEs (advanced lipoxidation end-products) on proteins is associated with aging and various diseases of oxidative stress, notably diabetes and its complications. Modification of protein to AGE/ALEs is known to be site-directed and this has potential implications for protein functionality and design of AGE/ALE inhibitors. Determination of the site-specificity of modification is achieved most efficiently by MS. The present paper summarizes some of the challenges that need to be addressed when determining the site-specificity of AGE/ALE formation on protein by MS, using the protein RNase as an example. The following topics are discussed: formation and significance of AGE/ALEs, location of glycated peptides, enzymic digestion of glycated peptides and selection of mass spectrometric settings of analysis for glycated peptides.
Ames
Jennifer M
JM
Human Nutrition and Health Group, School of Biological Sciences, Queen's University Belfast, Belfast BT9 5AG, Northern Ireland, UK. j.m.ames@queens-belfast.ac.uk
D017127:Glycation End Products, Advanced / Q000737:chemistry* / Q000378:metabolism; D015227:Lipid Peroxidation; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry*
D017127:Glycation End Products, Advanced; D010455:Peptides; D011506:Proteins