SYNTHESES OF LABELED HEMES FOR PROTEIN NMR STUDIES

用于蛋白质 NMR 研究的标记血红素的合成

• 批准号: 2883212
• 负责人: Kevin M Smith
• 金额: $ 23.39万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883212
• 关键词: Diels Alder reaction; Raman spectrometry; adduct; carbon; catalase; chemical synthesis; circular dichroism; cytochromes; deuterium; dimer; heme; heme oxygenase; hemoglobin; hemoprotein; hemoprotein structure; metalloproteins; myoglobin; nuclear magnetic resonance spectroscopy; photosensitizing agents; porphyrins; protein structure function; radiopharmacology; radiotracer; stable isotope

The objective of this proposal is discovery of fundamental chemistry and synthetic methodology for obtaining porphyrin systems of biological interest, with special emphasis on development of methodology for isotope labeling of hemes so as to provide access to unique spectroscopic probes of structure- activity relationships in heme proteins. Methodology will be developed which will permit synthesis of natural hemes regioselectively labeled in predetermined positions with deuterium, carbon-13, and nitrogen- 15, if sufficient is available, compounds resulting from these studies will subsequently be used for NMR, circular dichroism, and resonance Raman studies to gain an understanding of heme apoprotein interactions and structure/function relationships in a variety of biologically important heme proteins such as hemoglobins, myoglobins, cytochromes, oxygenases, and peroxidases. It is also proposed to synthesize a variety of meso- methylated hemes (for heme oxygenase studies), unlabeled heme analogues, heme dimers, and hydrohemes, as well as hemes with interrupted conjugation, isoporphyrin systems, and non-planar porphyrins of various types. We shall continue studies of reduced porphyrin systems known as porphodimethenes and shall further develop very simple, as well as more complex, methodology for obtaining porphyrin systems. Thr proposed work will provide a synthetic backbone and anchor point for spectroscopic methodology being developed to advance the understanding heme protein function, and of structural and electronic factors which cause several debilitating diseases such as anemias. Two fundamental approaches for synthesis of novel compounds will be developed; carbon-13, nitrogen-15, unlabeled porphyrins, and meso- methylporphyrins will be obtained by total synthesis from acyclic precursors. Some methods for such approaches have already been worked out, but improvements and discovery of new methodology, simple and multistep, is planned and anticipated. Some deuterium labeled, carbon-13 labeled porphyrins, protoporphyrin IX analogues, N-methyl- land meso- methylporphyrins and other hemes will be approached by manipulation of substituents on existing natural commercially available porphyrins.

这项提议的目的是发现基础化学和