CROSS-LINKERS FOR BIOMACROMOLECULES--BIS-(N,N-DIALKYL SULFONYLPROPENYLAMINES)

生物大分子交联剂--双-(N,N-二烷基磺酰丙烯胺)

• 批准号: 3789357
• 负责人: EARL DOOMES
• 金额: --
• 依托单位: SOUTHERN UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3789357
• 关键词: chemical chain length; chemical reaction; chemical synthesis; crosslink; cyclopentane; electrofocusing; gel electrophoresis; hemoglobin; medical education; minority institution research support; oxyhemoglobin; reagent /indicator; solubility

The title bifunctional (polyfunctional) organic reagents will be synthesized, and tested as cross-linkers of hemoglobin and oxyhemoglobin. Previously, two examples of the title compounds were characterized in our laboratory. The general approach that entails the regiospecific addition of 1,n-alkanedisulfonyl chloride to allyl chloride in a key step will be utilized. We shall extend the synthetic approach to include "ether" and "sulfone" functions in the "linkers" of reactive sites of the reagent. Hydrophilic functional groups in the "linkers" of the reactive sites, N,N- dialkyl 2-sulfonyl-1-amino-2-propenes, are expected to lead to significant levels of solubility in an aqueous environment. In our initial efforts, we shall synthesize two bifunctional organic reagents derived from a 1,5- disubstituted pentane: 1,5-bis-(N,N-diisopropyl 2-sulfonyl-1 -amino-2- propene)-3-oxapentane and 1,5-bis-(N,N-diisopropyl 2-sulfonyl-1-amino-2 propene)-3-thiapentene 3,3-dioxide. The design of this series of reagents allows us to vary the chemical reactivity and the length of the "linkers" in a systematic way. Chemical reactivities and selectivities of the organic cross-linking reagents will be assessed through an investigation of reactions (product studies and rate data) of the reagents with models of proteins and nucleic acids, hydrochlorides of amino acid esters and nucleotides (and/or their bases), respectively. Upon completion of the proposed studies, the effectiveness of the title reagents as cross linkers of hemoglobin and oxyhemoglobin will have been determined as a function of "linker" in length, solubility, and chemical reactivity. The selectivities and reactivities of the cross-linking reagents toward hemoglobin and oxyhemoglobin will be determined by isoelectric focusing and sodium dodecyl sulfate polyacrylamide gel electrophoresis. While this proposal focuses primarily on the development of crosslinking reagents for hemoglobin and oxyhemoglobin, the title compounds will be examined as modifiers of nucleic acids and histones.

标题双功能（多功能）有机试剂将是 合成并测试为血红蛋白和氧蛋白血红蛋白的交联。 以前，标题化合物的两个例子在我们的 实验室。需要加入的一般方法 在关键步骤中，在1，n- alalaldisulfonyl氯在关键步骤中将 利用。 我们将扩展合成方法以包括“以太”和 “硫酮”在试剂反应性位点的“接头”中起作用。 反应性位点的“接头”中的亲水官能团，n，n- 二甲基2-磺酮-1-Amino-2-丙烯酸苯甲酸杆菌有望导致显着 在水性环境中的溶解度水平。在我们的最初努力中，我们 应合成两种源自1,5-的双功能有机试剂 二烷二烷：1,5-双 - （n，n-二异丙基2-磺酮-1 -Amino-2- 丙烯）-3- oxapentane和1,5-双（N，N，N-二异丙基2-磺酮1-氨基-2） 丙烯）-3-硫烯3,3-二氧化物。这一系列试剂的设计 允许我们改变化学反应性和“接头”的长度 以系统的方式。化学反应性和选择性 有机交联试剂将通过研究评估 试剂的反应（产品研究和速率数据）与模型 蛋白质和核酸，氨基酸酯的盐酸盐和 核苷酸（和/或它们的碱基）分别。 完成后 拟议的研究，标题试剂作为交叉接头的有效性 血红蛋白和氧血红蛋白的含量将被确定为 长度，溶解度和化学反应性的“接头”。选择性 和朝着血红蛋白的交联试剂的反应性和 催产蛋白将通过等电聚焦和钠来确定 十二烷基硫酸聚丙烯酰胺凝胶电泳。 而这个建议 主要集中于开发的交联试剂 血红蛋白和催产蛋白，标题化合物将被检查为 核酸和组蛋白的修饰符。