Peptide resonance stabilization

An important factor in the structure of protein-DNA complexes can be the peptide backbone. The amide bond can fimction as an H-bond acceptor as well an H-bond donor. Due to the reduced flexibility of the backbone vs. side chain (resonance stabilization of the peptide bond), H-bonds to the peptide backbone lead to a rigid and tight arrangement in the complex and contribute extensively to the exact fit between protein and nucleic acid. 

Thiazolidine-4-carboxylic acid containing peptides exhibit an enhanced polar character when compared with most of the side-chain protected cysteine peptides. 139 The anomalously low nucleophilicity of its imino group (pATa = 6.24) in comparison to that of proline (pXa = 10.60) is due to the resonance stabilization of its unprotonated form 187188 This supposed resonance stabilization is supported by the X-ray crystal structure of 4-thiaproline.1 88 ... 

The peptide (—CO—NH—) groups in proteins are nearly planar because of resonance stabilization involving the C=0 and C—N bonds. 

Resonance stabilization of an amide accounts for its enhanced stability, the weak basicity of the nitrogen atom, and the restricted rotation of the C—N bond. In a peptide, the amide bond is called a peptide bond. It holds six atoms in a plane the C and O of the carbonyl, the N and its H, and the two associated a carbon atoms. 

In a mechanism involving nucleophilic catalysis, the enzyme would promote nucleophilic attack on the carbonyl carbon to produce a tetrahedral intermediate. In this intermediate, resonance stabilization of the C-N bond has been destroyed and the barrier to rotation about the C-N bond greatly reduced. Collapse of the tetrahedral intermediate with expulsion of nucleophile can produce either the cis or trans Xaa-Pro peptide. In the original work on PPI (Fischer et ai, 1984), results were presented that indicated that an enzyme sulfhydryl group was required for activity. This result was later interpreted to support a mechanism involving nucleophilic catalysis (Fischer et ai, 1989a,b). 

A second consequence of resonance stabilization is that all six atoms involved in the peptide bond lie in the same plane. All bond angles are -120° and the C=0 and N-H bonds are oriented 180° from each other. 

The resonance stabilization energy of the planar structure of the peptide bond is approximately ... 

Under suitable conditions the amine component (43 R6 = H) for peptide syntheses by a stereoselective Ugi reaction must be a good chiral template, i.e. it must have strong asymmetric inducing power, and it must be endowed with a group R5 that is cleavable from the 4CC product (86) under mild conditions. The search for a suitable chiral amine component (43 R6 = H) has been the most challenging subproblem in the development of peptide syntheses by stereoselective Ugi reactions.2 71 First, the resonance-stabilized vinylamines, e.g. ethyl (3-aminocrotonate (45), were tested as amine components, because their 4CC products are cleavable by mild acidolysis.45 In amines of the type (45) any center of chirality could, at best, be placed three bonds from the newly formed center of chirality. Accordingly, such amines would not be effective as chiral templates. 

The peptide bond can be written as a resonance hybrid of two structures (Figure 3.10), one with a single bond between the carbon and nitrogen and the other with a double bond between the carbon and nitrogen. The peptide bond has partial double bond character. As a result, the peptide group that forms the link between the two amino acids is planar. The peptide bond is also stronger than an ordinary single bond because of this resonance stabilization. 

The peptide group is planar as a result of resonance stabilization. This stereochemical feature determines a number of features of the three-dimensional structure of proteins. 

The C—C=0 and the C—N H groups must be in the same plane because of resonance stabilization of the double bond. Thus, on the basis of the measurements of bond distances resonance stabilization was suggested to occur. Indeed, while the normal C—N bond distance is 1.47 A, the actual distance determined by X-ray crystallography in the peptide bond is much shorter than expected (1.32 A). In the peptide bond, a n electron is associated with the C=0 bond and an isolated electron on the N atom. 

The VBSCE method has been used to probe the validity of the resonance model in organic chemistry following some controversies that appeared in the literature, regarding the presence or absence of resonance stabilization, for example, in the peptide bond, carboxylic acids, and enols. The enhanced acidity of carboxylic acids relative to alcohols is traditionally attributed to the stabilization of the carboxylate anion by delocalization of its 7t electrons via resonance structures 37-39 in Scheme 18. 

The carbonyl group of one amino acid and the amino group of the next by secondary amides called peptide bonds. The lone pair on the nitrogen of the peptide bond is delocahzed onto the carbonyl carbon, and the peptide bond is resonance stabilized. 

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