Biologically active proteins, peptides

Steber, W. D., Cady, S. M., Johnson, D. F., and Rice, T., 1993, Implant compositions containing a biologically active protein, peptide or polypeptide, European Patent AppHcation 523,330A1 (American Cyanamid Co., assignee). 

The domino process probably involves the chiral enamine intermediate 2-817 formed by reaction of ketone 2-813 with 2-815. With regard to the subsequent cy-doaddition step of 2-817 with the Knoevenagel condensation product 2-816, it is interesting to note that only a normal Diels-Alder process operates with the 1,3-bu-tadiene moiety in 2-817 and not a hetero-Diels-Alder reaction with the 1-oxa-l,3-butadiene moiety in 2-816. The formed spirocydic ketones 2-818/2-819 can be used in natural products synthesis and in medidnal chemistry [410]. They have also been used in the preparation of exotic amino adds these were used to modify the physical properties and biological activities of peptides, peptidomimetics, and proteins... 

The term polyproteins is used for two different types of entity. The first refers to precursor polypeptides which are cleaved post-translationally into biologically active proteins or peptides of quite different functions. Examples of these include polyproteins of viruses and some prohormones of vertebrates (reviewed in Kennedy, 2000b). The other type is large proproteins which comprise tandem repetitions of identical or similar polypeptides that are post-translationally cleaved into multiple copies of biochemically similar functional entities. The nematode polyprotein allergens/antigens (NPAs) fall into this class (Fig. 16.1). 

Bioteehnology produets differ in their method of preparation and potential problems they present in their formulation. Pharmacists involved in compounding with biologically active proteins are interested in their stabilization, formulation, and delivery. Most of the current biotechnology products are proteins, but soon some may be smaller peptide-like molecules. 

Mine Y, Kovacs-Nolan J. (2006) New insights in biologically active proteins and peptides derived from hen egg. World s Poultry SciJ 62 87-96. 

Traditional protein NMR spectroscopy of smaller proteins relies of 15N-filtered experiments, due to the relatively low expense of introducing 15N labels into proteins (compared to 13C) and the concomitant ability to use heteronuclear filtering to improve resolution in the H NMR dimension. Jelinek et al. were the first to demonstrate the ability to transfer this approach to peptides on TantaGel.80 They also showed the ability to detect pronounced peptide structure through the appearance of strong NOE correlations in 3H NOESY HRMAS spectra as shown in Fig. 8. This had important implications for the search of biological activity in peptides attached to supports, as the structure on the support may be different or more pronounced than in solution, if present at all in solution in peptides of this small size. 

TABLE 15.3 Other potential biological activities from peptides derived from various fish proteins... 

Besides peptides, marine organisms have been reported to produce biologically active proteins, which are probably involved in the protection of organisms against physiological and stress conditions. Recently, these molecules have been cloned from sponges [324] and marine microorganisms [325],... 

Morris, M. C., Depollier, J., Mery. J., et al. A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nature Biotechnol. 19 1173—1176, 2001. 

The synthesis of unnatural amino acids and peptides is of great interest since it offers the possibility to design new biologically active protein analogues. One of the possible interesting transformations is side chain oxidation of amino acids, for which MTO can be used. It is reported that various /V-Boc protected amino acids such as methionine (Met), cysteine (Cys), and tryptophan (Trp) can be oxidized with the MT0/H202 system [108]. 

The polymer reagent method has been used in peptide synthesis by other investigators also 95 -97). The method has been applied to the synthesis of a number of medium-sized peptides and biologically active protein sequences 98). 

The polymeric active ester method has been used successfully for the preparation of several small- to medium-sized peptides in very pure form the potentiality of the method has also been illustrated by the synthesis of a number of biologically active protein sequences like bradykinin 106), thyrotropin-releasing hormone 107), ACTH sequences 105), and LH—RH 108> in good overall yields. 

Examination of the action of proteolytic enzymes on native proteins (or biologically active peptides) can yield two important types of information. First, determination of the susceptibility of particular bonds in a protein substrate offers a means for evaluation of certain features of the conformation of the protein (Linderstr0m-Lang, 1952 Mihalyi and Harrington, 1959). Second, proteolysis can serve as an important method for modification of the covalent structure of biologically active proteins (Anfinsen and Redfield, 1956). 

The stability of biotechnology-produced products, proteins (macromolecules), and peptides is unique when compared with conventional pharmaceuticals (small molecules). Protein degradation by both chemical and physical processes leads to the loss of biological activity, whereas peptides decompose only through chemical instability with loss of efficacy and produce undesirable biological effects. 

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