Our aim, in this proposal, is to continue our research efforts to chemically and structurally characterize purified human tracheobronchial glycoproteins. Primary emphasis is placed on analyzing the major sulfated oligosaccharides and the major oligosaccharide-oligopeptide subunits isolated from tracheobronchial glycoproteins. The focus of this proposal stresses the characterization of the sulfated oligosaccharides since it is primarily this fraction that increases with severity of a lung disease. Tracheobronchial glycoproteins and isolated fractions from patients suffering from various forms of chronic obstructive pulmonary disease (e.g., chronic bronchitis, asthma, bronchiectasis, alveolar proteinosis and cystic fibrosis (CF)) will be studied, their structures elucidated and compared so as to gain insight from different pathological vectors on how the tracheobronchial submusocal glands alter their secretory glycoprotein structure in response to chronic disease. Since the start of the initial proposal, we have made substantial and significant progress in elucidating the structures of many sulfated oligosaccharides. We propose to continue this exciting work, in addition to enhancing our research efforts in analyzing the different oligosaccharide-oligopeptide fractions isolated from tracheobronchial glycoproteins. Gas-liquid chromatography and mass spectrometry will be employed in all chemical investigations which will also include several new analytical techniques developed during the initial proposal period for the analysis of amino and neutral sugars, amino acids and carboxylates. Our knowledge of the structure and related functions of tracheobronchial glycoproteins is still very poor. Over the past two years we have made significant findings; discovering several new sulfated structures. We are gradually beginning to unravel the basic structure of these complex, large molecular weight glycoproteins. Continuation of this research is important so that we can understand the structure/function biochemistry of these very important molecules in health and disease.
