NEW METHODOLOGY FOR GLYCOPROTEINS

糖蛋白是自然界中最重要、分布最广的生物活性物质之一 药剂，用于调节广泛的基本生物功能。 尽管如此，它们的结构可以简化为四个基本要素 “核心”，作为主干，可以添加其他糖。 以达到观察到的生物学特性。我们所了解的 它们的特殊性受到以下事实的限制：实验室制备 路线并不是现成的。 这些实验室准备的问题，在 鉴于目前疯狂地寻找艾滋病疫苗的情况 许多药物化学家正在从事这项工作。为此，杜克大学的调查人员 大学医学中心将注意力集中在信封上 HIV病毒的糖蛋白(GP-120)，以及他们与我们的讨论 确定高甘露糖型糖蛋白为主要目标 人工合成的征服。 一项文献调查表明，美国面临的主要问题是 高甘露糖糖蛋白的合成可分为四类 类别：1)与低聚糖组装有关的问题 部分；2)受控地创造了麻烦的贝塔连接 甘露糖和N-乙酰氨基葡萄糖残留物；3)安装 在异常中心普遍存在天冬酰胺残基，以及4) 多肽链的精加工。 为实现这四个目标而制定的战略是 概述。我们的方法在很大程度上依赖于正戊烯基的化学 糖苷作为一种新的激活异常中心的方法 各种偶联反应。杜克大学的汤姆·马修斯教授 医疗中心将为我们提供所需的任何多肽(见上文第4项)。 虽然我们的综合战略的发展将集中在 GP-120候选疫苗，需要强调的是，方法学要 应探索的糖蛋白应适用于多种糖蛋白。这个 如上所述，核心结构的存在确保了我们的 方法论不会局限于一个给定的目标。

Glycoproteins are among nature's most important and wide-spread bioactive agents, serving to regulate a wide range of essential biological functions. In spite of this, their structures can be simplified to give four basic "cores" which serves as backbones to which other sugars can be added in order to achieve the observed biological specificities. Our knowledge of their specificities is limited by the fact that laboratory preparative routes are not readily available. These problems of laboratory preparation, take on added significance at the present time in view of the frantic search for an AIDS vaccine in which many medicinal chemists are engaged. To this end investigators at Duke University Medical Center have focussed attention on the envelope glycoprotein (gp-120) of the HIV virus, and their discussions with us have identified the high-mannose-type of glycoprotein as a primary target for synthetic conquest. A survey of the literature suggests that the major problems confronting the syntheses of high-mannose glycoproteins can be divided into four categories: 1) problems associated with the assembly of the oligosaccharide moiety; 2) the controlled creation of the troublesome beta-linkage between mannose and the N-acetylglucosamine residues; 3) the installation of the ubiquitous asparagine residue at the anomeric center, and 4) the elaboration of the peptide chain. The development of strategies for tackling these four objectives is outlined. Our approach depends heavily on the chemistry of n-pentenyl glycosides as a novel method for activation of the anomeric center towards various coupling reactions. Professor Tom Matthews of the Duke University Medical Center will supply us with any peptides needed (see item 4 above). Although our development of synthetic strategies will be focussed on the gp-120 vaccine candidate, it should be emphasized that the methodology to be explored should be applicable to a wide variety of glycoproteins. The existence of core structures, as described above, ensures that our methodology will not be confined to a given target.