Protein biological activity

Today the word peptide imphes much more than simply a chain of amino acids. Even in nature, peptides are composed of more than the 20 amino acids that are the building blocks of proteins. Biologically active peptides contain d- as well as L-amino acid residues. Peptides are glycosylated, phosphorylated, myristoylated, farnesylated, palnoitoylated, sul-fated, and N-alkylated, and are even present in more complex conjugates. 

Gonz ilez-Diaz, H., Molina, R., Uriarte, E. (2004). Markov entropy backbone electrostatic descriptors for predicting proteins biological activity. Bioorganic Medicinal Chemistry Letters, 14, 4691. 

Proteins are polymers of amino acids. The term protein is only used for those assemblies having more than 50 amino acids. Protein biological activity is not manifested in assembhes containing less than this number of residues. Hence, the term polypeptide is normally used to refer to such molecular assemblies. The biofunctionality of the protein molecules owes its origin to many factors of which the conformation is an important component. The conformational state of proteins can be divided into 4 hierarchical levels ... 

The protein folding problem is the task of understanding and predicting how the information coded in the amino acid sequence of proteins at the time of their formation translates into the 3-dimensional structure of the biologically active protein. A thorough recent survey of the problems involved from a mathematical point of view is given by Neumaier [22]. 

GAs or other methods from evolutionary computation are applied in various fields of chemistry Its tasks include the geometry optimization of conformations of small molecules, the elaboration of models for the prediction of properties or biological activities, the design of molecules de novo, the analysis of the interaction of proteins and their ligands, or the selection of descriptors [18]. The last application is explained briefly in Section 9.7.6. 

Protein tertiary structure is also influenced by the environment In water a globu lar protein usually adopts a shape that places its hydrophobic groups toward the interior with Its polar groups on the surface where they are solvated by water molecules About 65% of the mass of most cells is water and the proteins present m cells are said to be m their native state—the tertiary structure m which they express their biological activ ity When the tertiary structure of a protein is disrupted by adding substances that cause the protein chain to unfold the protein becomes denatured and loses most if not all of Its activity Evidence that supports the view that the tertiary structure is dictated by the primary structure includes experiments m which proteins are denatured and allowed to stand whereupon they are observed to spontaneously readopt their native state confer matron with full recovery of biological activity... 

The posterior lobe of the pituitary, ie, the neurohypophysis, is under direct nervous control (1), unlike most other endocrine organs. The hormones stored in this gland are formed in hypothalamic nerve cells but pass through nerve stalks into the posterior pituitary. As early as 1895 it was found that pituitrin [50-57-7] an extract of the posterior lobe, raises blood pressure when injected (2), and that Pitocin [50-56-6] (Parke-Davis) causes contractions of smooth muscle, especially in the utems (3). Isolation of the active materials involved in these extracts is the result of work from several laboratories. Several highly active posterior pituitary extracts have been discovered (4), and it has been deterrnined that their biological activities result from peptide hormones, ie, low molecular weight substances not covalendy linked to proteins (qv) (5). 

Sulfoxide hGH. Methionine residues in proteins are susceptible to oxidation primarily to the sulfoxide. Both pituitary-derived and biosynthetic hGH undergo sulfoxidations at Met-14 and Met-125 (29). Oxidation at Met-170 has also been reported in pituitary but not biosynthetic hGH. Both desamido hGH and Met-14 sulfoxide hGH exhibit full biological activity (29). 

The indole ring is incorporated into the stmcture of the amino acid tryptophan [6912-86-3] (6) and occurs in proteins and in a wide variety of plant and animal metaboUtes. Much of the interest in the chemistry of indole is the result of efforts to understand the biological activity of indole derivatives in order to develop pharmaceutical appHcations. 

Through combined effects of noncovalent forces, proteins fold into secondary stmctures, and hence a tertiary stmcture that defines the native state or conformation of a protein. The native state is then that three-dimensional arrangement of the polypeptide chain and amino acid side chains that best facihtates the biological activity of a protein, at the same time providing stmctural stabiUty. Through protein engineering subde adjustments in the stmcture of the protein can be made that can dramatically alter its function or stabiUty. 

Proteins and Meals. Nutritional properties of the oilseed protein meals and their derived products are deterrnined by the amino acid compositions, content of biologically active proteins, and various nonprotein constituents found in the defatted meals. Phytic acid (3), present as salts in all four meals, is beheved to interfere with dietary absorption of minerals such as 2inc, calcium, and iron (67) (see Food toxicants, naturally occurring Mineral nutrients). ... 

The amide linkage between monomer units in a protein is called a peptide bond. Peptides and polypeptides, which often exhibit biological activity (see Antibiotics, peptides Neuroregulators), are smaller than proteins. Although the differentiation between polypeptide and protein is somewhat arbitrary, the usual distinction is drawn around 100 monomer units. Proteins are also characterized by higher levels of stmcture resulting from internal interactions. 

In HIC, the hydrophobic interactions are relatively weak, often driven by salts in moderate concentration (I to 2 M), and depend primarily on the exposed residues on or near the protein surface preservation of the native, biologically active state of the protein is an important feature of HIC. Elution can be achieved differentially by decreasing salt concentration or increasing the concentration of polarity perturbants (e.g., ethylene glycol) in the eluent. 

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