Peptides stability enhancement

The addition of PEG to the gels was critical because the PEG chains participate in the macromolecular complexes, function as a peptide stabilizer and enhance the mucoadhesive characteristics of the gels. In this work, strong dose-dependent hypoglycemic effects were observed in healthy and diabetic rats following oral administration of these gels. 

Peptoids are oligomers of A-substituted glycines that, similar to P-peptides, have enhanced stability toward proteolysis and can be used in the design of new biological probes and in drug discovery. Peptoids are typically synthesized via the submonomer approach that features iterative acylation and amination reactions as shown in Scheme 9.6. This can take up to 3 h per monomer unit, and longer pep-toid sequences exacerbate this problem. Monomer incorporation can be reduced to... 

The incorporation of unnatural amino acids into peptides to enhance their metabolic stability and activity is an area of major interest in peptidomimetic chemistry. In order to accomplish this goal. Park and colleagues have developed nucleophilic substitutions of a-bromo amides derived from L-amino acids in the presence of amine nucleophiles on the basis of DKR processes. Whereas moderate stereoselectivities were obtained when using benzylamine as the nucleophile, the nucleophilic substitution reactions of various a-bromo amides with the more sterically demanding secondary amine nucleophile, dibenzylamine, allowed the stereoselectivity of the reactions to be increased remarkably. This methodology provided, in the presence of tetra-n-butyl-ammonium iodide (TBAI) and TEA, the corresponding dipeptide analogues in up to 98% yield and 98% de (Scheme 1.15). 

An alternative linker strategy recently employed in the synthesis of stapled peptides is through the incorporation of a triazole bridge, which was constructed through azido-acetylene click chemistry. These new stapled peptides offer enhanced chemical stability and further resistance to proteolysis [49c]. The linker length in these triazole bridge stapled peptides has a similar requirement as the hydrocarbon stapled peptide. 

As mentioned earlier, short peptides tend to form random coils rather than an a-helix structure and not all the stapled peptides stabilize the a-helices. Circular dichroism (CD) spectroscopy is commonly used to measure the a-helix conversion enhancement of the stapled peptides. The helical content is direcdy proportional to ellipticity ([0]) or the rotation at a wavelength of 222 nm [61] therefore, the percentage of helicities can be calculated from molar ellipticities at 222 nm ([flJzzz) using —31500 (l-2.57/ ) and 0 deg cm /dmol as the values for 100 and 0% heUcity, respectively, where is the number of amino acid residues in the peptide [61]. 

Clearly, experiments with whole plants are required to address some of these issues. Now that a class of antifungal peptides with enhanced stability against plant... 

Phalloidin and phallacidin are cyclic peptides from the mushroom Amanita phalloides that stabilize F-actin. Phalloidin binds to residues 114-118 of an actin protomere and blocks nucleotide exchange without interfering with nucleotide hydrolysis. It enhances the rate of nucleation as well as that of elongation. It slowly penetrates the cell membrane and is used for immunocytochemical localization of F-actin. 

Some proteins contain covalent disulfide (S— S) bonds that link the sulfhydryl groups of cysteinyl residues. Formation of disulfide bonds involves oxidation of the cysteinyl sulfhydryl groups and requires oxygen. Intrapolypeptide disulfide bonds further enhance the stability of the folded conformation of a peptide, while interpolypeptide disulfide bonds stabilize the quaternary structure of certain oligomeric proteins. 

Such one-center enhancement effects can be illustrated by formamide 5 for nb—>7Ta (3.109c) interactions. As shown in Table 3.19, the n — -7tco interaction of 5 leads to strong conjugative stabilization (59.8 kcal mol-1) and reduced C—O bond order (1.732), the famous amide resonance of peptide chemistry ... 

The major strategies to enhance transmucosal peptide and other drug absorption include (a) coadministration with protease inhibitors, (b) the use of membrane permeation enhancers, (c) coadministration with a combination of absorption enhancers and protease inhibitors, (d) modification of peptide structure to improve metabolic stability or membrane permeation, and (e) use of nano- or microparticles [27], Some of these strategies have been investigated using the in situ rat model. 

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