Discovery research elucidating structures

Prior to the advent of electrospray ionization (ESI), the primary use of mass spectrometry in natural product discovery was the structural elucidation of compounds that had been isolated with bioassay-guided fractionation. With the advent of commercial ESI and atmospheric-pressure chemical ionization (APCI) sources in the early 1990s [74,75], researchers gained access to LC-MS instrumentation that could be used to directly analyze natural product mixtures. This allowed the integration of mass spectrometry into the earliest stages of natural product discovery. The impact of ESI and APCI on natural products discovery has been the subject of recent reviews [76,77]. 

X-ray analysis. In the pantheon of methods employed to elucidate structures, single-crystal Z-ray analysis reigns supreme. It deserves every chemist s respect for it unites speed, completeness, and dependability. Using a modem diffractometer for measurements and a computer for calculations, this method unequivocally establishes within a few days or weeks the composition and solid-state conformation of a small molecule. By contrast, 150 years separated the discovery of the notorious alkaloid poison strychnine and the confirmation of its complex structure by synthesis, which in 1947 culminated a half-century s chemical research. 

Soon after the monumental discovery and elucidation of the structure of ferrocene, the homo- and copolymerization of vinylferrocene was reported using a number of different catalysts." The solution and bulk synfliesis of polyvinylferrocene (1) has been studied in detail, as have the properties of polyvinylferrocene. While many of these studies were undertaken in the 1960s and 1970s, the polymerization of vinylferrocene continues to be an active area of research. The copolymerization of vinylferrocene with styrene using a living radical initiator (viz., TEMPO) was also reported. ... 

Merck Research Laboratories, Discovery Predinical Sciences, Global Chemistry—Structure Elucidation Group, Summit, New Jersey, 07901, USA... 

Proteases, since their discovery, have played an important role in both basic and applied research because their sometimes exquisite selectivity of peptide bond cleavage can be extremely useful in the elucidation of other proteins structures and function. The following three sub-sections give several examples of how proteases are used in specific aspects of research. 

One path of research resulting from the discovery of ferrocene has been concerned with the synthesis and structural elucidation of cyclopentadienyl derivatives of other metals and metalloids. At the present time, over 60 chemical elements have been found to form one or more cyclopentadienyl compounds. This topic has recently been reviewed by the present author as well as by others (17, 83, 125). 

Two major discoveries in 1953 were of crucial importance in the history of biochemistry. In that year James D. Watson and Francis Crick deduced the double-helical structure of DNA and proposed a structural basis for its precise replication (Chapter 8). Their proposal illuminated the molecular reality behind the idea of a gene. In that same year, Frederick Sanger worked out the sequence of amino acid residues in the polypeptide chains of the hormone insulin (Fig. 3-24), surprising many researchers who had long thought that elucidation of the amino acid sequence of a polypeptide would be a hopelessly difficult task. It quickly became evident that the nucleotide sequence in DNA and the amino acid sequence in proteins were somehow related. Barely a decade after these discoveries, the role of the nucleotide... 

Following Zamecnik s discovery that ribosomes are the complexes responsible for protein synthesis, and following elucidation of the genetic code, the study of ribosomes accelerated. In the late 1960s Masayasu Nomura and colleagues demonstrated that both ribosomal subunits can be broken down into their RNA and protein components, then reconstituted in vitro. Under appropriate experimental conditions, the RNA and protein spontaneously reassemble to form 30S or SOS subunits nearly identical in structure and activity to native subunits. This breakthrough fueled decades of research into... 

Soon after the discovery of RNase Ti, it was suggested (70, 71) that it would become an important tool for the elucidation of nucleotide sequence in RNA. Indeed, since 1962 several workers have tried to use the enzyme for the nucleotide sequence analysis of RNA, especially in highly purified specific tRNA s. Finally, the brilliant research of Holley and his associates in 1965 resulted in the first elucidation of the complete nucleotide sequence of an RNA, alanine specific yeast tRNA, using RNase Ti as a main tool (29). Since then many successful elucidations of nucleotide sequence of various RNA s, using RNase Ti as a main tool, followed, and now the enzyme is well-known as an essential tool for the structural analysis of RNA. 

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