NEW METHODOLOGY FOR GLYCOPROTEINS

糖蛋白是自然界中最重要和最广泛的生物活性物质之一， 试剂，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的 “核心”作为骨架，其他糖可以加入其中。 以实现观察到的生物学特异性。 我们的知识 它们的特异性受到实验室制备 没有现成的路线。 实验室准备的这些问题，在 目前，鉴于对艾滋病疫苗的疯狂研究， 许多药物化学家都在工作。 为此，杜克大学的研究人员 大学医学中心把注意力集中在信封上 糖蛋白（gp-120）的艾滋病毒，他们的讨论与我们有 确定了高甘露糖型糖蛋白作为主要目标， 合成征服 对文献的一项调查表明， 高甘露糖糖蛋白的合成可分为四种 类别：1）与寡糖组装相关的问题 2）控制性地产生麻烦的β-连接， 甘露糖和N-乙酰葡糖胺残基; 3）安装 异头中心普遍存在的天冬酰胺残基，和4） 肽链的精细加工。 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n-戊烯基的化学性质 糖苷作为一种新的方法，用于活化的异头中心， 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肽（见上文第4项）。 虽然我们的合成策略的发展将集中在 GP-120候选疫苗，应该强调的是， 应该适用于各种各样的糖蛋白。 的 核心结构的存在，如上所述，确保我们的 方法论不会局限于某一特定目标。

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.