Systematic efforts are currently under way to construct defined sets of cloned genes for high-throughput expression and purification of recombinant proteins To facilitate subsequent studies of protein function, we have developed miniaturized assays that accommodate extremely low sample volumes and enable the rapid, simultaneous processing of thousands of proteins A high-precision robot designed to manufacture complementary DNA microarrays was used to spot proteins onto chemically derivatized glass slides at extremely high spatial densities The proteins attached covalently to the slide surface yet retained their ability to interact specifically with other proteins, or with small molecules, in solution Three applications for protein microarrays were demonstrated: screening for protein-protein interactions, identifying the substrates of protein kinases, and identifying the protein targets of small molecules

http://science.sciencemag.org/content/sci/289/5485/1760.full.pdf

Printing proteins as microarrays for high-throughput function determination.

Chemistries that Facilitate Nanotechnology Kim E. Sapsford,† W. Russ Algar, Lorenzo Berti, Kelly Boeneman Gemmill,‡ Brendan J. Casey,† Eunkeu Oh, Michael H. Stewart, and Igor L. Medintz*,‡ †Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States ‡Center for Bio/Molecular Science and Engineering Code 6900 and Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States Sotera Defense Solutions, Crofton, Maryland 21114, United States

Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology.

Bioorganometallic Chemistry of Ferrocene

The high affinity of the noncovalent interaction between biotin and streptavidin forms the basis for many diagnostic assays that require the formation of an irreversible and specific linkage between biological macromolecules. Comparison of the refined crystal structures of apo and a streptavidin:biotin complex shows that the high affinity results from several factors. These factors include the formation of multiple hydrogen bonds and van der Waals interactions between biotin and the protein, together with the ordering of surface polypeptide loops that bury the biotin in the protein interior. Structural alterations at the biotin binding site produce quaternary changes in the streptavidin tetramer. These changes apparently propagate through cooperative deformations in the twisted beta sheets that link tetramer subunits.

https://science.sciencemag.org/content/sci/243/4887/85.full.pdf

Structural origins of high-affinity biotin binding to streptavidin.

Summary: The discovery of novel small-molecule antibacterial drugs has been stalled for many years. The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort. The major challenges fall into two areas: (i) proper target selection, particularly the necessity of pursuing molecular targets that are not prone to rapid resistance development, and (ii) improvement of chemical libraries to overcome limitations of diversity, especially that which is necessary to overcome barriers to bacterial entry and proclivity to be effluxed, especially in Gram-negative organisms. Failure to address these problems has led to a great deal of misdirected effort.

Challenges of Antibacterial Discovery

Phosphonomycin is a newly discovered antibiotic produced by streptomycetes. It is effective, when administered by the oral route, to mice infected with Gram-positive or Gram-negative microorganisms. The antibiotic is bactericidal and inhibits cell-wall synthesis.

https://science.sciencemag.org/content/sci/166/3901/122.full.pdf

Frank J. Wolf

Papers

Phosphonomycin, a New Antibiotic Produced by Strains of Streptomyces

The properties of streptavidin, a biotin-binding protein produced by streptomycetes.

Plasma cholesterol lowering action of bile acid binding polymers in experimental animals.

D-4-amino-3-isoxazolidone, a new antibiotic*

Compositions and method for binding bile acids in vivo including hypocholesteremics