Research/development protein relationships

Today, it is well-known that peptides or proteins exhibit various kinds of taste. Our group has been researching on the relationship between taste and structure of peptides, BPIa (Bitter peptide la, Arg-Gly-Pro-Pro-Phe-Ile-Val) (7 as a bitter peptide, Om-p-Ala-HCl (OBA), Om-Tau-HCl as salty peptides(2j, and "Inverted-Aspartame-Type Sweetener" (Ac-Phe-Lys-OH) as a sweet peptide(5). The relationship between taste and chemical structure was partly made clear. Since commercial demand for these flavor peptides is increasing, we need to develop new synthetic methods which can prepare these peptides in large scale. We developed the following two methods (1) protein recombination method as a chemical method, (2) enzymatic synthesis using chemically modified enzyme as a biochemical method. 

The molecular and genetic relationship between enzyme induction and repression was clarified by the genetic research of Jacob and Monod at the Pasteur Institute, Paris (see reference l7>). Their classic work led them to develop the operon hypothesis for the control of protein synthesis in prokaryotes, which has since been verified by direct biochemical experiments. 

Based on these mechanisms a new frontier in the application of enzymes to biotechnology, including the development of synthetic enzymes (synzymes)82,83 will be exploited. Research on structure-function relationships between ribozymes and abzymes will lead to the development of a number of sequence specific catalysts, which will control expression of a specific gene or its products, and eventually to application as pathogen controls in agriculture and to clinical use. Sequence specific abzymes may also facilitate research on the primary structure determination of protein. 

Protein chemical modification is a problem-solving technique in research and technology. Modifications also occur in natural deteriorations. Generally these modifications are with the most reactive side chains and are predominantly oxidations, reductions, and nucleophilic and electrophilic substitutions. Deteriorations include peptide bond scissions, racemizations, fi-eliminations, and formation of products by the reaction of proteins with added chemicals. Proteins are modified intentionally for structure-function relationship studies or for development of new and improved products. Although appearing quite varied, the techniques used in pharmacological, food and feed, or other industrial areas differ more operationally than from major differences in the levels of chemical sophistication that are used. 

In addition to extending the utility of analytical NMR, these developments have had a direct impact on screening methodologies, where NMR spectroscopy may now be used directly as a rapid and sensitive method for the characterization of binding affinities of mixtures of compounds in combinatorial libraries.3,9 11 A powerful screening method based on observation of NMR signals from a protein target has been developed by researchers at Abbott laboratories.12 Termed SAR (structure-activity relationship) by NMR, this technique has proved to be extremely valuable for the identification of novel lead compounds. 

Chapter 3 provides an overview of physicochemical factors that impact analysis and purification of polypeptides and proteins by HPLC techniques. The current status and some of the future challenges facing this major field of separation sciences are considered from both didactic and practical perspectives (Chapter 3). This chapter attempts to provide an overview of terms, concepts, principles, practical aspects, and primary references that underpin the recent developments in this field. Where appropriate, key relationships and dependencies that describe the interactive behavior of polypeptides and proteins with chemically immobilized ligands are discussed. This understanding is central to any subsequent exploration of alternative avenues now available for further research and development into the field of polypeptide or protein purification and analysis. 

NLP techniques provide the basis to extract this kind of more detailed information. In the past years approaches have been developed that are mainly focused on the biomedical domain to extract protein-protein interactions60 and gene-disease relations.61 They are based upon the correct recognition of the named entities taking part in the relationship. Dedicated patterns have to be developed to identify all the phrasal constructs that are indicative of relationships between chemical and biomedical entities available in text being of interest for academic researchers and the pharmaceutical industry. 

The structure/activity relationship (SAR) tools employed in odor research are essentially the same standard tools used in all applications, and the models developed fall into the categories of substrate and receptor models. The pharmaceutical industry is the leader in SAR techniques, and the fragrance industry tends to follow its lead. Early models were substrate based, but the discovery of the genes that code for the olfactory receptor proteins has also allowed receptor models to be constructed. 

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