| abstract |
The present invention is directed to diagnostic and therapeutic methods based on the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by administering a molecule having a hydrophilic loop domain, which domain in lysozyme and lactoferrin is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to methods and compositions for partitioning AGEs away from a sample. The invention is also directed to methods for determining a prognosis of AGE complications in a patient suffering from an AGE-associated disease or disorder by measuring the level of activity of antibacterial proteins, such as lysozyme and lactoferrin, in a biological sample from a subject. Decreased levels of antibacterial protein bacteriocidal activity may be indicative of increased levels of AGEs, and a prognostic indicator of increased susceptibility to bacterial infection. In a further aspect, the invention relates to detection of AGEs in a biological sample. In specific embodiments, AGEs inhibit the bacteriocidal activity of lysozyme and lactoferrin, and 17 or 18 amino acid hydrophilic loop peptides bracketed by cysteine (the first and last amino acids are cysteine that form a disulfide bond) bind to AGE-bovine serum albumin. |