Peptides elongation

Figure 38-8. Diagrammatic representation of the peptide elongation process of protein synthesis. The small circles labeled n - 1, n, n -I-1, etc, represent the amino acid residues of the newly formed protein molecule. EFIA and EF2 represent elongation factors 1 and 2, respectively. The peptidyl-tRNA and aminoacyl-tRNA sites on the ribosome are represented by P site and A site, respectively.

The solution methods require orthogonal protection of the C- and N-termini of the N- or O-glycosyl amino acid or peptide as well as of the glycan throughout the synthesis. Furthermore, protection of the C- and N-termini should both be of the temporary type, which can be removed under mild selective conditions to have the peptide elongated in either direction. 

The temporary protecting group should be readily removed to allow peptide elongation. 

The spontaneous formation of piperazine-2,5-diones occurs mainly during N-deprotection or the acylation step to dipeptide esters (usually unhindered esters such as Me, Et, Bzl, and Pac esters) that contain an TV-alkyl amino acid especially at the C-terminusJ152 In some cases the formation of piperazine-2,5-diones becomes the major reaction product and thus prevents peptide elongation by the [1+2] or [1+3] segment condensation strategy in solution synthesis or elongation of the peptide from the C-terminus in SPPS. Piperazine-2,5-dione formation... 

As one of the characteristics of t t[CH2NH] replacement is the introduction of a new basic site, protection of the secondary amine can be required during peptide elongation. However, it has been shown by Coy and co-workers that the tp[CH2NH] surrogate is generally resistant to further acylation, except for the incorporation of the Gly residue, probably due to a steric factor J7 8 In the case of pseudopeptide libraries, protection of the secondary amine seems to be important for affording products in better yields and purity.[9]... 

In this section we consider peptide analogues containing the amide surrogates 1 to 11 (Scheme 1). These can be isosteric with the amide group in the sense that consecutive a-carbons are separated by three bonds, as in link 1, the (nitrono) peptides, and link 2, the [methyleneamino(hydroxy)] or (TV-hydroxy reduced amide) peptides. They also can be an N-modified amide, as in link 3, the (TV-hydroxy amide) peptides, and link 4, the (V-aminoamide) peptides. Elongation of the peptide unit by one covalent bond has been realized by the introduction of a heteroatom or a methylene into the backbone, as in link 5, the (hydrazide) peptides, link 6, the (amidoxy) peptides, link 7, the (oxomethyleneamino) peptides, link 8, the [(hydroxy)ethyleneamino] peptides, link 9, the (ethyleneamino) peptides, and link 10 the (oxime) peptides. Finally, insertion of an ethylenic bond (two covalent bonds) between the a-carbon and the carbonyl gives rise to link 11, the (but-2-enamide) or (vinylogous amide) peptides. 

The possibilities of N-(dialkylphosphoryl)amino acids for the prebiotic syntheses of peptides and polynucleotides have been studied in a series of papers [24,116-122], However, it must be emphasized that the phosphoryl group does not behave as an amino-activating group, the hydrolysis of which would be coupled to peptide bond formation. Actually, further peptide elongation requires the subsequent hydrolysis of the N-terminal phosphoryl group of the ligated product. In the presence of an amino acid ester, dipeptide esters 16 with an unreacted N-phosphoryl protection are formed, support-... 

This unexpected consequence of the efficient reaction of carbon dioxide can be expressed in an other way NCAs can be considered as the most activated amino acid species achievable in water in the environment of the primitive Earth. The only exception would be species bearing a chemical protection of the a-amino groups that are unlikely because peptide elongation would have been complicated by the necessity of an additional deprotection step. From a prebiotic perspective, there is consequently no need to search for activated amino acid derivatives with a degree of activation higher than NCAs (thermodynamic limit in Fig. 3). 

In this synthetic scheme, the reactions for peptide elongation are carried out in homogeneous solutions, while the product of each reaction is isolated and briefly purified in solid form with free oligosaccharides serving as phase tags. It... 

Interestingly, these crystal structures also make it possible to understand more subtle differences among the inhibitory effects of different macrolides. As a peptide elongates, the portion of the macrolide it first encounters will be the sugar branch that extends from C5 of the lactone ring (Fig. 4.6) towards the peptidyl... 

Stepwise Peptide Elongation Using Fmoc Protocols... 

It inhibits initiation and peptide elongation during protein synthesis. [Haskell et al. J Am Chem Soc 81, 3480, 3482 1959, Hichens Rinehart/Am Chem Soc 85 1547 1963, Beilstein 18 III/IV 7534.]... 

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