Peptide amido groups

In Chapt. 4, we have examined the hydrolysis of a variety of amido groups occurring in drugs and other xenobiotics. As we saw in Chapt. 5, cyclic amides (i.e., lactams) constitute a class of special interest in medicinal chemistry. The present chapter is dedicated to another class of amides of even greater medicinal and biochemical interest, namely that of peptides. 

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

Acl residues 20-21. This is the only Cys-Asx sequence in the A chain there is 1 amido group in this peptide, so it must be Cys-Asn ... 

In order to obtain dual-action agents, the imidazotetrazines, mitozolomide and temozolomide combined with a P-lactam antibiotic were synthesized <02EJM323>. Carboxylic acids derived from the amido groups of these imidazotetrazines have been conjugated to simple aminoacids and peptides by carbodiimide coupling <02JMC5458>. 

Proteins, on the other end of the scale of molecular complexity, act as emulsifiers but behave differently from the small molecules, because of their individual molecular structures, and, indeed, it is the particular proteins present which give many food emulsions their characteristic properties. Most, if not all, proteins in their native states possess specific three-dimensional structures which are maintained in solution, unless they are subjected to dismptive influence such as heating (6). When they adsorb to an oil-water interface, it is unlikely that the peptide chains of proteins dissolve significantly in the oil phase, as they are quite hydro-philic as a result of the presence of carboxyl or amido groups it is more likely that the major entities penetrating the interface are the side chains of the amino acids (Table 1). It is possible, for example, for an a-helical portion of a protein to have a hydrophobic side, created by the hydrophobic side chains which lie outside the peptide core of the helix. However, even proteins lacking such regular structures possess amino acids with hydrophobic side chains which will adsorb to the oil-water interface. When a protein is adsorbed, the structure of the protein itself will... 

The majority of examples of metal-assisted hydrolysis of peptides which have been reported recently involve the use of cobalt(II) centers. However, use of copper(II) for the specific hydrolysis of the C-terminal residue of polypeptides has been reported. The polypeptides coordinate to the copper with concomitant deprotonation of the amido group of the C-terminal residue. Treatment with persulfate results in an oxidative decarboxylation to yield an iV-acylimine, which undergoes subsequent hydrolysis to generate a carbonyl compound and carboxamide. This results in an overall process, Eq. (3). In contrast, treatment with [IrCl ] results in the alternative reaction (4), although this process is dependent upon the redox potential of the copp r(II)/copper(III) couple. 

DNA-Protein. A large number of proteins in nature perform their function by expediting electron transfer, and there is an extensive literature on electron transfer through proteins (see Refs. 122-124 for reviews). Relevant here are the observations that the excess electron has a large range (not readily trapped) [125] while the hole is relatively immobile (trapped by deprotonation at the peptide bond giving amido radicals) [126]. This raises the expectation that electrons but not holes could be transferred from protein to DNA. This has been observed by a number of groups [127-131]. 

Coupling of 4-(4-hydroxymethyl-3-methoxyphenoxy)-butyric acid (HMPB, for synthesis of peptide acids) or p-[(R S)-a-[l- (9H- fluorenyl- methoxyform-amido]- 2,4- dimethoxybenzyl] - phenoxyacetic acid (modified Rink linker, for synthesis of carboxamide peptides) linkers to MBHA resin For Fmoc chemistry several types of solid supports are available, which include hydroxymethyl-based, aminomethyl-based, and trityl chloride resins. We describe the use of the MBHA resin. In this case the respective linker (to achieve peptide acid or amide) is coupled to the resin and first amino acid is then coupled to the linker. Attachment of the linker to the resin is a reaction between the carboxyl-group of the linker and amino-group of the MBHA resin. Commercially available resins with linkers already attached could also be used. 

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