Peptide framework

The complexity of the problem is shown by the same author using an example of a completely different type. Without the help of an enzyme, Chu and Orgel (1999) were able to form a peptide bond between two cysteine residues, which were bonded to a cysteine-containing peptide framework. In this case, the activation was carried out using a classical condensation agent (carbodiimidazole), which can certainly not be considered prebiotic, but the yields of dicysteine (25-60%) were amazing The framework peptide had the structure... 

Fig. 5.4 The reaction cycle for the formation of the dipeptide cysteinylcysteine on a peptide framework (Chu and Orgel, 1999)...

The two functional groups forming the peptide bond are brought close together by their positioning on the peptide framework, so that bond formation occurs readily. 

The application of CPO, HRP and CiP is limited to sterically unencumbered substrates and all these peroxidases produce the same absolute configuration of the chiral hydroperoxide. To overcome this limitation, the semisynthetic enzyme selenosubtilisin, a mimic for glutathione peroxidase, with the peptide framework of the serine protease subtilisin was developed by Bell and Hilvert. This semisynthetic peroxidase catalyzes the reduction of hydrogen peroxide and hydroperoxides in the presence of 5-mercapto-2-nitrobenzoic acid. It was utilized by Adam and coworkers and Schreier and coworkers for the kinetic resolution of racemic hydroperoxides (equation 17) . The results obtained were very promising. 

The important difference between linear and cyclic peptides is the reduced conformational flexibility imposed by the cyclization. 14,151 Cyclic peptides have, therefore, been under intense investigation with respect to their conformational preferences 30,31 and their different turn motifs, e.g. reverse turns. 32 35 To differentiate between the structural influences of the numerous sequence elements the following special concepts have been described 161 (1) Global constraints are structural characteristics that restrict the whole molecule, e.g. the macrocyclic structure of the peptide framework and (2) local constraints comprise a large number of structure-inducing building blocks, such as proline, D-amino acids, and turn mimetics. 

To design photo-induced electron transfer devices, the group of Nishino [69] reported the preparation of a bis-a-helical nanostructure, 74. The peptidic framework was designed to orient rigidly in space the redox triad, composed of a Ru2 + complex, an anthraquinone, and two propylviologens, when incorporated in a lipid bilayer (Fig. 28). Although the compound exhibited a strong a-helical content in methanol, its conformation in a vesicle bilayer was different and undetermi ned. Nevertheless, irradiation of the Ru(II) complex of 74 resulted in a slow electron transfer. 

Fig. 30. The development of a synthetic decarboxylase (81) [74], An a-helical peptide framework orients correctly several amino groups for the catalysis of the decarboxylation of 82. (Reproduced with the permission of Ref. 1)...

Voyer, N., Lamothe, J. (1995). The use of peptidic frameworks for the construction of molecular receptors and devices. Tetrahedron, 51 9241. 

Recently, we have addressed a problem previously described concerning the relationship between morphine and enkephalin. The inherent mobility of the enkephalin linear peptide framework, its rapid degradation in vivo, and the existence of multiple receptor subtypes, have hampered the assessment of its bioactive conformations. Conformationally constrained peptides or pepti-domimetics should facilitate this task. Several turn conformations have been proposed based on computational models,X-ray crystallography and spectroscopic studies. " - - ... 

It is known that proteins can incorporate porphyrin units by embedded them into their peptidic frameworks [170]. With such systems, the polypeptidic shells modulate the response of the porphyrin units to the external environment. Non-natural counterparts of these biologically occurring systems can be generated by embedding one or more porphyrin systems inside dendritic frameworks. Indeed, several dendrimers incorporating porphyrin cores have been designed and synthesized already [171,172]. 

Most of the large-scale multiporphyrin systems found in nature are situated within peptide frameworks, and their relative configurations and orientations are held fast with noncovalent interactions between protein residual groups and the chromophores. The advantages of the use of noncovalent interactions is twofold (1) a variety of noncovalent interactions having different characteristics is available for assembling molecules into a large-scale... 

Since the introduction of the first peptide organocatalyst in the 1980s, a considerable number of new peptide frameworks have been developed that are able to effectively catalyse several important transformations including alcohol esterifications, 1,4-conjugate additions, aldol reactions, Strecker synthesis, asymmetric cyanohydrin synthesis and alkene epoxidation are discussed. A few successful examples of solid-supported peptides and reactions in ball milling under solvent-free conditions have been demonstrated. These methods combine the advantages of being economically and environmentally friendly processes. 

Pires MM, Przybyla DE, Chmielewski J (2009) A metal-collagen peptide framework for three-drm siraial cell culture. Angew Chem Int Ed Engl 48 7813-7817. doi 10.1002/anie. 200902375... 

Roy S, Shinde S, Hamilton GA, Hartnett HE, Jones AK (2011) Artificial [FeFe]-hydrogenase on resin modification of an amino acid to anchor a hexacarbonyldiiron cluster in a peptide framework. Eur J Inorg Chem 7 1050-1055. doi 10.1002/ejic.201000979... 

The effects of host-guest substitutions within a given difficult peptide framework (50,51). 

Enzymes are comprised of proteins which have definitive primary structures that can organize into secondary, tertiary and even quaternary structures. The enzyme consists of a peptide framework that contains cavities in which the catalytically reactive centers are incorporated. The enzyme protein is typically about 20-40 nm in size. The catalytically reactive centers can be part of the peptide that builds the enzyme framework such as carboxylic acid groups, or consist of cationic centers such as the porphyrins or nonreducible cations as Zn " " or Mg " " directly attached to the protein cavity. As mentioned earlier, the external part of the enzyme is hydrophilic and the internal microcavity is hydrophobic, with the possible exception of the often polar reaction center. In enzymatic reactions, the match between shape and size of reactant or product and catalytic center cavity is important. 

Upon reaction with a substrate molecule, the shape of the enzyme is altered. The flexibility of the peptide framework implies that changes in overall protein shape (induced, for instance, by allosteric effects) may affect the shape of the reaction center. This will... 

Optimization of reaction complex topology implies the positioning of charged enzyme groups such that there is an optimum interaction with (activated) reactants. Significant protonation (in protolytic enz5unes) or electron transfer (in redox catalysis) can already occiu in the adsorbed state. This is due to the unique electrostatic properties of the enzyme, which is shielded from the solvent by its hydrophobic peptide framework. 

While limited examples of metal-peptide frameworks exist, the ability to prepare both flexible and rigid MOFs with unusual functionality and properties, without incorporating secondary co-ligands, makes them materials... 

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