Specificity secondary structural

The structural proteins give extracellular structures mechanical stability, and are involved in the structure of the cytoskeleton (see p. 204). Most of these proteins contain a high percentage of specific secondary structures (see p. 68). For this reason, the amino acid composition of many structural proteins is also characteristic (see below). 

Furthermore, the sulfonamide bond is expected to possess enhanced metabolic stability with structural similarities to the tetrahedral transition state involved in amide bond enzymatic hydrolysis, thus making sulfonamide peptides interesting candidates in the development of protease inhibitors and new drugs. The oligomers and polymers should also be interesting molecular scaffolds, with specific secondary structures enforced by hydrogen bonding)100,101 ... 

As shown in the catalytic reactions, the formation reactions and others, the asymmetric reactions of synthetic polypeptides are characterized by the participation of specific secondary structures. Such influence of the secondary conformation on the asymmetric reaction is considered to have a general importance in relation not only to the stereospecificity of the reaction of enzyme, but also to a possible way by which present-day enzymes obtained their high stereospecificity in the ctxirse of chemical evolution. 

Table 2.2 Kinds of Conformational Constraints Leading to Specific Secondary Structures for Peptide Hormones and Neurotransmitters...

Because the targets for hormones and neurotransmitters are integral membrane proteins such as G-protein-coupled receptors (GPCRs), the hormones will bind to these proteins with specific secondary structures. 

Polypeptide molecules of course exhibit many more vibrational frequencies than the half-dozen or so amide modes. For example, a molecule as simple as the extended form of polyglycine has about 50 bands in its IR and Raman spectra. It is clear that the information contained in the entire spectrum must therefore be a more sensitive indicator of three-dimensional structure. The only way to utilize this information fully is through a normal-mode analysis, that is, by comparing observed frequencies with those calculated for specific secondary structures. This can provide a powerful method for testing structural hypotheses in great detail. 

Pharmaceutical companies are increasingly interested in developing products based on proteins, enzymes, and peptides. With the development of such products comes the need for methods to evaluate the purity and structural nature of these biopharmaceuticals. Proteins, unlike traditional pharmaceutical entities, rely on a specific secondary structure for efficacy. Methods to monitor the secondary structure of pharmaceutically active proteins, thus, is necessary. Infrared spectroscopy provides a way to study these compounds quickly and easily. Byler et al. (65) used second-derivative IR to assess the purity and structural integrity of porcine pancreatic elastase. Seven different lyophilized samples of porcine pancreatic elastase were dissolved in D20, placed in demountable cells with CaF2 windows, and IR spectra obtained. The second derivatives of the spectra were calculated and the spectral features due to residual water vapor and D20 removed. 

The minimum number of amino acids required to form a P-sheet is usually 6-7 and around 12-13 for an a-helix. For such small peptides it is possible to predict the specific secondary structure (a-helix, P-sheet, P-tum) as well as the orientation of side chains (Fig. 9.2.12), thereby allowing an efficient design. For shorter peptides the conformational equilibrium is displaced towards the unordered coil, and for large peptides predictions are still impossible. 

Owing to the well-defined stereochemistry, the diversities in choosing hydropbobic/hydrophilic amino acids, and specific secondary structures, polypeptides have been intensively investigated as a biomaterial.Contrary to the random hydrophobically driven self-assembly of the most synthetic polymer, the secondary structures of the polypeptides such as a-helix, /3-sheet, and random coil significantly affect the gelation behavior. 

Off-lattice minimalist models are similar to the lattice models in that they generally use a simplified amino acid representation. Rather than being confined to a lattice, the protein is free to move in continuous space. As with lattice models, many different off-lattice models have been studied. Some are meant to be reduced models of specific proteins,whereas others are meant to capture a specific secondary structure motif, such as an a-helix, a p-sheet, or an a-p sandwich (see citations in Ref. 81). As before, we will focus on a few representative models and provide appropriate references about the others. 

In the following examples, peptides are conjugated to hydrophobic polymers. These differ from lipidation in that the hydrophobic blocks can be larger and can adopt specific secondary structures, which influences the characteristics of the self-assembled structures. 

Fibrillar proteins have a specific secondary structure. For example, the basic secondary structure of keratin consists of two pairs of closely linked right-handed a-hehces (a superhehx) that are coiled into a left-handed hehx. The basic secondary structure of collagen is a triple hehx in which the left-handed polypeptide helix is coiled into the right-handed superhehx. 

AUG codon during interaction with mRNA s. Apparently, there are 6-10 nucleotides (Fig. 20 Revel et al, 1970, 1973), or the region with a specific secondary structure near the AUG codon (Steitz, 1969) which is defined as the signal of in-itiation -S. It was also demonstrated that both initiatory factors, F2 and F3, participated in the binding of mRNA s with 30S ribosomes. 

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