When studying a biological structure, ' it is frequently important to identify a componentor specific site. An elegant way to achieve 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 (EK, 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 fi-agments, multienzyme complexes, and viruses and phages, and c) Exploring the use of these labels by EK atomic force microscopy (AFK, scanning tunneling microscopy (STIM), electron energy loss spectroscopy (EELS), 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 fimding for such applications. Several gold clusters (An. , and Aul.4.)Itungstate clusters (WI I), and a larger uranium complex have been developed winch have proven useful in studying various biological structures by EM. They also have been used to develop improved immunolabels. 'Me clusters can be covalently coupled to a variety of finictional groups such as thiols, amines, carboxyls, phosphates, or carbohydrates. This endeavor will provide unique- high-resolution structural information about specific functional sites that is difficult or impossible to obtain by other means.
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