Lectins for Detection of Altered Glycosylation of Circulating Glycoproteins

Abstract

Human α-1-antitrypsin (α-1-anti-T), one of the most important serum protease inhibitors, is a glycoprotein of mol wt 51,000 (1-3).α-1-anti-T neutralizes the activity of enzymes such as elastase, trypsin, and chymotrypsin The molecule consists of a single polypepide chain of 394 amino acids, with three sugar chains that are N-linked to asparagine residue at positions 46, 83, and 247 (2-4).The major chemical structures of the sugar chains have been reported to be biantennary and triantennary oligosaccharides (4,5) Genetic polymorphism of α-1-anti-T has been elucidated by many investigators. About 40 genetic variants have been recognized, implying considerable heterogeneity and polymorhism. These complexities include variations in the degree of sialylation on the sugar chains and complex formation with low molecular weight thiols by disulfide bridges of the reactive single cysteine (6) Hereditary deficiency of α-1-anti-T predisposes to degenerative lung disease and liver disease (7,8).Nucleotide sequence studies of α-1-anti-T have shown single or two-base substitution or dinucleotide deletion with subsequent single amino acid substitutions or deletions. In the common S and Z variants, A to T (264 Glu to Val) and G to A (342 Glu to Lys) mutations were identified (9).