When studying a biological structure, it is frequently important to identi~ a component or specific site. An elegant way to aclileve this is to use labels that tag specific sites or subunits. This work focuses on: a) Development of small, high-resolution labels that may be visualized by electron microscopy ~M), x-ray scattering, or other means, b) Application of these labels to a variety of biological structures including transfer RNA (tRNA) and ribosomes, chaperonins, blood-clotting proteins and complexes, RNAse P, chromosomes, DNA fragments, multienzyme complexes, and viruses and phages, and c) Exploring the use of these labels by EM, atomic force m'croscopy (AFM), scanning tunneling microscopy (STM), electron energy loss spectroscopy ~ELS), and synchrotron x-ray anomalous scattering. Some of these new labels may have application in medicine, e.g., for cancer therapy, but this grant does not cover flinding for such applications. Several gold clusters (An1 and Au1.4~), tungstate clusters (W11), and a larger uranium complex have been developed which have proven useftil in studying various biological structures by EM. They also have been used to develop improved immunolabels. The clusters can be covalently coupled to a variety of flinctional groups such as thiols, amines, carboxyls, phosphates, or carbohydrates. This endeavor will provide unique high-resolution structural information about specific flinctional sites that is difficult or impossible to obtain by other means.
Showing the most recent 10 out of 101 publications
