TRACHEOBRONCHIAL GLYCOPROTEIN STRUCTURE

我们的目标，在这个建议中，是化学和结构表征， 纯化的人气管支气管糖蛋白。 重点放在 分析主要的酸性硫酸化低聚糖和主要的 从气管支气管分离的寡糖-寡肽亚单位 糖蛋白 硫酸化低聚糖的表征研究 强调，因为它主要是这一部分，随着严重程度的增加， 肺部疾病 气管支气管糖蛋白和分离组分 从患有各种形式的慢性阻塞性肺疾病的患者 肺病（例如，慢性支气管炎，哮喘，支气管扩张， 肺泡蛋白沉积症和囊性纤维化（CF）将被研究，映射， 比较，以便从不同的病理载体中了解如何 气管支气管粘膜下腺分泌糖蛋白发生改变 慢性疾病的反应。 Accent也被放在 分析分离的不同寡糖-寡肽亚基， 气管支气管糖蛋白 我们的初步研究强烈表明 在蛋白质核心中有确定的氨基酸序列 用于连接的寡糖的硫酸化或唾液酸化， 是寡糖类型的差异， 与丝氨酸和苏氨酸相连。 气液色谱和质谱 光谱法将用于所有化学研究，并将包括新的 方法，在这个实验室开发的，用于分析硫酸盐，糖 硫酸盐、唾液酸、氨基糖和氨基酸。 这些糖蛋白的阴离子性增加的一个可能作用是， 慢性肺部疾病是，它使他们不太容易受到 细菌酶降解 我们建议调查这一点， 体外研究气管支气管糖蛋白的抗性， 具有不同程度的硫酸化，以糖苷酶攻击。 到目前为止，我们对结构和相关知识知之甚少。 气管支气管糖蛋白的功能。 在过去的五年里，我们 分离和纯化了所有的气管支气管糖蛋白， 其中的一部分，将在本提案中使用。 他们的研究将提供 重要和必要的信息的结构和生物化学 这些对健康和疾病非常重要的分子。

Our aim, in this proposal, is to chemically and structurally characterize purified human tracheobronchial glycoproteins. Emphasis is placed on analyzing the major acidic sulfated oligosaccharides and major oligosaccharide-oligopeptide subunits isolated from tracheobronchial glycoproteins. Research on characterizing the sulfated oligosaccharides is stressed since it is primarily this fraction that increases with severity of a lung disease. Tracheobronchial glycoproteins and isolated fractions from patients suffereing from various forms of chronic obstructive pulmonary disease (e.g., chronic bronchitis, asthma, bronchiectasis, alveolar proteinosis and cystic fibrosis (CF) will be studied, mapped and compared so as to gain insight from different pathological vectors on how the tracheobronchial submucosal glands alter their secretory glycoprotein structure in response to chronic disease. Accent is also placed on analyzing the different oligosaccharide-oligopeptide subunits isolated from tracheobronchial glycoproteins. Our preliminary studies strongly suggest that there is definite amino acid sequence in the protein core that codes for sulfation or sialation of the attached oligosaccharide and that there is a difference in the type of oligosaccharide that is glycosidically linked to serine and to threonine. Gas-liquid chromatography and mass spectrometry will be employed in all chemical studies and will include new methods, developed in this laboratory, for the analysis of sulfate, sugar sulfates, sialic acids, amino sugars and amino acids. One possible role for the increased anionicity of these glycoproteins in chronic lung disease is that it renders them to be less susceptible to bacterial enzymatic degradation. We propose to investigate this by studying in vitro the resistance of tracheobronchial glycoproteins, possessing varying degrees of sulfation, to glycosidase attack. To date, we have very little knowledge of the structure and related functions of tracheobronchial glycoproteins. Over the past five years we have isolated and purified all the tracheobronchial glycoproteins, and fraction thereof, to be used in this proposal. Their study will provide important and needed information about the structure and biochemistry of these very important molecules in health and disease.