Protein modifications, survey

Spatola A. Peptide backbone modifications. A structure-activity analysis of peptides containing amide bond surrogates conformational constraints and related amide bond replacements. In Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins A Survey of Recent Developments, Vol. 7. Weinstein B, ed. 1983. Marcel Dekker Inc., New York. pp. 267—357. 

While the majority of metal-mediated protein modifications covered in this survey involve activation of small molecules (e.g. O2, H2O) by metal complexes, there are some instances in which complexation of the metal ion itself serves as the mechanism of modification. Complexes with low-valent cobalt and chromium undergo relatively rapid ligand exchange, permitting solution complexes to coordinate with exposed amino acid side chains (e.g. histidine) on the surface of proteins. Oxidation of this adduct converts the complex to a substitution-inert species. The extreme inertness of Cr(III) and Co (Iff) complexes toward ligand-substitution... 

DNA is ideally suited as a structural material in supramolecular chemistry. It has sticky ends and simple rules of assembly, arbitrary sequences can be obtained, and there is a profusion of enzymes for modification. The molecule is stiff and stable and encodes information. Chapter 10 surveys its varied applications in nanobiotechnology. The emphasis of Chapter 11 is on DNA nanoensembles, condensed by polymer interactions and electrostatic forces for gene transfer. Chapter 12 focuses on proteins as building blocks for nanostructures. 

The subject of protein chemistry is too large to be surveyed systematically in one chapter. Various examples of chemical modifications are covered nonsystem-atically throughout this volume in discussions of individual enzymes and methods. To aid in locating these examples, some are listed in Table 9.1. 

Proteomics is concerned with the analysis of the complete protein complements of genomes. Thus proteomics includes not only the identification and quantification of proteins, but also the determination of their localization, modifications, interactions, activities, and functions. This chapter focuses on protein sequences as the sources of biochemical information. Protein sequence databases are surveyed. Similarity search and sequence alignments using the Internet resources are described. 

Thioredoxin in Regulation of Calvin Cycle Enzymes Motohashi and colleagues used thioredoxin as a hook to fish out from plant extracts the proteins that are activated by thioredoxin. To do this, they prepared a mutant thioredoxin in which one of the reactive Cys residues was replaced with a Ser. Explain why this modification was necessary for their experiments. [Motohashi, K., Kondoh, A., Stumpp, M.T., Hisabori, T. (2001) Comprehensive survey of proteins targeted by chloroplast thioredoxin. Proc. Natl. Acad. Sci. USA 98, 11,224-11,229.]... 

The protein identification or sequence determination of a protein can be achieved using two different approaches top-down [22, 23] and bottom-up [24], A top-down experiment involves high-resolution measurement of an intact molecular weight and direct fragmentation of protein ions by tandem mass spectrometry (MS/MS) [25], This approach surveys an entire protein sequence with 100% coverage. Post-translational modifications such as glyco-... 

In the development of proteins as therapeutic agents, it is crucial to ensure the homogeneity of the potential products. However, a survey of the current literature has indicated that overexpression of recombinant proteins in E. coli often leads to translational errors as well as post-translational modifications (1). Acetylation of the e-amino group of lysyl residues in bovine somatotropin has been documented (2). Substitution of methionine by norleucine is another well known example (3,4). 

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