Peptide chains elongation

Pharmacology Tigecycline, a glycylcycline, inhibits protein translation in bacteria by binding to the 308 ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. 

Erythromycin acts by binding to the 50S subunit by an unknown mechanism. It works in the same way as chloramphenicol by inhibiting translocation, where the elongated peptide chain attached to tRNA is shifted back from the aminoacyl site to the peptidyl site. Erythromycin was used against penicillin-resistant staphylococci, but newer penicillins are now used for these infections. It is, however, the drug of choice against legionnaires disease . 

Fig. 1.15. Structure of an elongated peptide chain. Carbon, Q oxygen, O nitrogen, o hydrogen and side chain...

Elongation is a cycUc process on the ribosome in which one amino acid at a time is added to the nascent peptide chain. The peptide sequence is determined by the order of the codons in the mRNA. Elongation involves several steps catalyzed by proteins called elongation factors (EFs). These steps are (1) binding of aminoacyl-tRNA to the A site, (2) peptide bond formation, and (3) translocation. 

These agents bind selectively to a region of the SOS ribosomal subunit close to that of chloramphenicol and erythromycin. They block elongation of the peptide chain by inhibition of peptidyl transferase. 

Glycopeptides containing a 2-acetamido-N-(L-aspart-4-oyl)-2-deoxy-/ -D-glucopyranosylamine residue (11) may be synthesized either by direct addition of the carbohydrate residue to the peptide chain, or by elongation of the peptide chain from 11 in the direction of the carboxylic, or the amino, terminal. 

Elongation of the peptide chain in the direction of the N-terminal by a solid-phase procedure was introduced by Lavielle and coworkers,132 who prepared the glycopeptide [3-0-(2-acetamido-2-deoxy-/ -D-gluco-pyranosyl)-L-serine]-L-glycyl-L-alanine (189) by first coupling 168, de-protected by hydrogenolysis, to an L-alanyl resin (188), and, after re-... 

Methods of Selective Deprotection, Followed by Peptide-Chain Elongation... 

AGGREGATION DURING PEPTIDE-CHAIN ELONGATION AND SOLVENTS FOR ITS MINIMIZATION... 

Afterward, the peptide chain was elongated following the standard Fmoc-based protocol. Before cleavage of the peptide the incorporated Mmt-protected cysteine was deprotected using 1% TFA. Under these very mild conditions the farnesyl moiety was not harmed. Palmitoylation could he achieved using an excess of palmitoyl chloride. Cleavage with copper acetate and methanol as a nucleophile gave the farnesylated and palmitoylated N-Ras sequence with the C-terminal methyl ester 78. ... 

After translation has been initiated (see p. 250), the peptide chain is extended by the addition of further amino acid residues (elongation) until the ribosome reaches a stop codon on the mRNA and the process is interrupted (termination). 

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