Amide bond in peptides

The amide bonds in peptides are usually called peptide bonds, and they are formed between C(l) of one amino acid and N(2) of another (sometimes called eupeptide bonds). Peptides may also include compounds linked by other amide bonds (sometimes called isopeptide bonds). 

A peptide is any compound produced by amide formation between a carboxyl group of one amino acid and an amino group of another. The amide bonds in peptides are called peptide bonds. The word peptide is usually applied to compounds whose amide bonds (sometimes called eupeptide bonds) are formed between C-1 of one amino acid and N-2 of another, but it includes compounds with residues linked by other amide bonds (sometimes called isopeptide bonds). Peptides with fewer than about 10-20 residues may also be called oligopeptides those with more residues are called polypeptides. Polypeptides of specific sequence of more than about 50 residues are usually known as proteins, but authors differ greatly on where they start to apply this term. 

The amide bonds in peptides and proteins can be hydrolyzed in strong acid or base Treatment of a peptide or protein under either of these conditions yields a mixture of the constituent amino acids. Neither acid- nor base-catalyzed hydrolysis of a protein leads to ideal results because both tend to destroy some constituent ammo acids. Acid-catalyzed hydrolysis destroys tryptophan and cysteine, causes some loss of serine and threonine, and converts asparagine and glutamine to aspartic acid and glutamic acid, respectively. Base-catalyzed hydrolysis leads to destruction of serine, threonine, cysteine, and cystine and also results in racemization of the free amino acids. Because acid-catalyzed hydrolysis is less destructive, it is often the method of choice. The hydrolysis procedure consists of dissolving the protein sample in aqueous acid, usually 6 M HC1, and heating the solution in a sealed, evacuated vial at 100°C for 12 to 24 hours. 

The most common way to form the amide bond in peptide synthesis uses dicyclo-hexylcarbodiimide (DCC) as the coupling agent ... 

The reaction of an acid and an amine with DCC is often used in the laboratory to form the amide bond in peptides, as is discussed in Chapter 28. 

The amide bonds in peptides and proteins are called peptide txinds. 

Peptide bond (Section 28.5) The amide bond in peptides and proteins. 

Acylation of amide bonds in peptides can be accomplished by silylation with trimethylsilyl chloride followed by treatment with acid chlorides. A modified procedure has been applied to acylation of the sensitive 3-lactam antibiotic cephamycin, where silylamides like trimethylsilylurethane trap generated HCl (equation 54). ... 

Partial hydrolysis by aqueous acid is a regioselective amide-cleavage process, although it does not relate to a particular amide bond the most easily hydrolysed amide bond in a polyamide is the one that is most exposed to reagents or otherwise enhanced in its propensity to hydrolysis. Partial hydrolysis was an important feature of the earliest structure determinations for peptides (e.g., by Sanger see Chapter 5), and currently features in a method for mass-spectrometric structure determination of peptides (Section 4.11). The alkylation of the amide bond in peptides, described in Chapter 5, assists mass-spectrometric study through increasing the volatility of peptides. 

The ECD process, by its nature, is a very rapid process and bond dissociation occurs faster than the redistribution of intramolecular vibrational energy that occurs with CID. This explains the dissociation of the strong N-C, amine bonds in the presence of the weaker C—N amide bonds in peptides and proteins.93,94 Consequently, any labile PTMs (e.g., phosphorylation, sulfation, 7-carboxylation, N- and O-glycosylation) are preserved and may be unequivocally located in the peptide/protein sequence. See also discussion in Section 9.10.3.2.6 on the use of ECD/ETD and CID/IRMPD for protein/peptide sequencing, and Table 4. 

Takeuchi, Y., and Marshall, G. R. (1998) Conformational analysis of reverse-turn constraints by N-methylation and N-hydroxylation of amide bonds in peptides and non-peptide mimetics. J. Am. Chem. Soc. 120, 5363-5372. 

A related group of acylases catalyzes amide formation and hydrolysis. Aspergillus is one source of such enzymes. One class of substrates is made up of di- and triesters with a-heteroatom substituents. Such substrates show selectivity for the carboxy group that is a to the heteroatom, which is the position analogous to the amide bond in peptides. 

Problem 20.19. The amide bond in peptides does not have the properties of a single bond. There is no free rotation about the carbon-nitrogen bond and the bond length is shorter than expected for a single bond. The CO — N bond is said to have considerable double-bond character. Describe how resonance theory rationalizes the double-bond properties of the amide bond. 

L. Zhu and N. M. Kostic, Toward artificial metallopeptidases mechanisms by which platinum(II) and palladium(II) complexes promote selective, fast hydrolysis of unactivated amide bonds in peptides, Inorganic Chemistry, vol. 31, no. 

Hydrolysis (or solvolysis) of peptides and proteins involves addition of a water (or solvent) molecule across an amide bond in peptide backbones without modifying side chain structures (Fig. 2). The hydrolytic approach generates native C-terminal carboxy and N-terminal amino groups. Hence, it is particularly useful and straightforward in protein sequencing, proteomics, and protein engineering applications. 

Use of RP(0Ph)2 as dehydrating agent in forma -tion of amide bonds in peptide synthesis. Condensing agent is hydrolyzed in the process. 

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