Formation of Peptide Bonds

Of the biochemical reactions of amino acids, the most important is the formation of peptide bonds. 

If prebiotic peptides and/or proteins were in fact initially formed in aqueous solution (the hypothesis of biogenesis in the primeval ocean ), the energy problems referred to above would have needed to be solved in order for peptide synthesis to occur. As discussed in Sect. 5.3, there is some initial experimental evidence indicating that the formation of peptide bonds in aqueous media is possible. An important criterion for the evolutionary development of biomolecules is their stability in the aqueous phase. The half-life of a peptide bond in pure water at room temperature is about seven years. The stability of the peptide bond towards cleavage by aggressive compounds was studied by Synge (1945). The following relative hydrolysis rates were determined experimentally, with the relative rate of hydrolysis for the dipeptide Gly-Gly set equal to unity ... 

Using experimental conditions similar to those described above, Huber and Wachtershauser were able to detect the formation of peptide bonds in reactions involving three amino acids the main product, however, was only a dipeptide. 

Benesch, R., and Benesch, R.E. (1956) Formation of peptide bonds by aminolysis of homocysteine thiol-actones./. Am. Chem. Soc. 78, 1597. 

Figure 6.10 Structures of amino acids having overall net charges at pH 7.0. In proteins, the charges associated with the a-amino and a-carboxyl groups in all but the terminal amino acids are not present, as these groups are directly involved in the formation of peptide bonds...

JH Jones. The formation of peptide bonds a general survey, in The Peptides Analysis, Synthesis, Biology, Vol. 1, pp 65-104. Academic Press, New York, 1979. 

Fig. 3.4. Formation of peptide bonds by peptidases under special in vitro conditions...

The ribosome is both the site of protein synthesis and an active participant in the process. The eukaryotic ribosome is constructed from two subunits the smaller 40S subunit and the larger 60S subunit. Basically, the 40S subunit binds the mRNA and monitors the recognihon between the mRNA codon and tRNA anticodon. The 60S subunit has the binding sites for aminoacyl-tRNAs and catalyzes the formation of peptide bonds. Remarkably, the catalytic entity for peptide bond formahon in the 60S subunit is the RNA component, not the protein component. Therefore, the 60S subunit acts as a ribozyme. 

Both the LINK and the BOND constraints are ideal for specifying or excluding the chemistry at a particular bond. For example, one could easily exclude the formation of peptide bonds between specific components to generate peptidomimetics. However, the most prevalent use is to eliminate bonded heteroatoms or other unstable chemical species. 

As we shall see in the next chapter, some natural RNA molecules catalyze the formation of peptide bonds, offering an idea of how the RNA world might have been transformed by the greater catalytic potential of proteins. The synthesis of proteins would have been a major event in the evolution of the RNA world, but would also have hastened its demise. The informationcarrying role of RNA may have passed to DNA because DNA is chemically more stable. RNA replicase and reverse transcriptase may be modem versions of enzymes that once played important roles in making the transition to the modern DNA-based system. 

Tetracycline and tetracycline derivatives (see Table 33-3) inhibit protein synthesis by binding to several components of the ribosomal apparatus in susceptible bacteria.3,12 Hence, these drugs may cause misreading of the mRNA code, as well as impair the formation of peptide bonds at the bacterial ribosome. Thus, tetracyclines are very effective in preventing bacterial protein synthesis. 

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