Chain elongation, stepwise

The stepwise polymerisation of activated amino acids leads to the formation of activated dimers, which very often cyclise to diketopiperazines and are thus removed from the chain elongation process (Orgel, 1989). 

Preparation of BAL-anchored peptide-resins by on-resin reductive amination followed by stepwise chain elongation... 

PREPARATION OF BAL-ANCHORED PEPTIDE RESINS BY ON-RESIN REDUCTIVE AMINATION, FOLLOWED BY STEPWISE CHAIN ELONGATION (SCHEME B)... 

With the C-terminal residue introduced as part of the BAL anchor and the penultimate residue incorporated successfully by the optimized acylation conditions just described, further stepwise chain elongation by addition of Fmoc-amino acids generally proceeded normally by any of a variety of peptide synthesis protocols. 

A multi-step reaction sequence was then realized to prepare the precursor (178) for the pivotal macrocyclization reaction. Alternate stepwise chain elongations were achieved according to Schemes 28 and 29. Reaction of the tosylate prepared from the alcohol 162 with lithium acetylide afforded the alkyne 174 (Scheme 28). Following the introduction of a tosylate at the upper branch, a one-carbon chain elongation of the terminal alkyne afforded the methyl alkynoate 175. A methyl cuprate 1,4-addition was used to construct the tri-substituted C double bond stereoselectively. For this purpose, the alkynoate 175 was initially transformed into the Z-configured a,/ -unsat-... 

Scheme 28 Stepwise chain elongation toward the macrocycle...

Due to the low reactivity of the nitrogen, incorporation of the pyroglutamic acid into endo-positions by stepwise chain elongation is difficult (see reft49 and refs cited therein). It may be achieved using suitably protected aminoacyl-pyroglutamic acid derivatives as dipeptide synthons. These are accessible in satisfactory yields, e.g. by acylation of pGlu-OBzl with N-protected amino acid pentafluorophenyl esters in the presence of NaH or LiHMDS. 49 ... 

The precursor tetratosylamide 22 may be prepared in five steps from ethylenediamine. The reaction sequence (Scheme 3.7) involves diacylation of ethylenediamine with 3-thiadiglycollic anhydride, followed by esterification, ammonolysis, borane reduction and toluenesulfonylation.12 This stepwise synthesis of the desired tetratoluenesulfonamide involving a simple chain elongation strategy is reminiscent of the syntheses of large ring aza-oxa crowns (e.g. [24]-N404) discussed in Chapter 2. 

The )9-ketoacyl-synthases/acyltransferases (KS/ AT) in each module effect the chain elongation by methyl-malonyl-coenzyme A units catalyzing a Claisen e.ster condensation followed by decarboxylation (Scheme 2). Subsequent domains are module-specific ketoreductases (KR), dehydratases (DH) or enoyl-reductases (ER), which regulate the functionalization of the newly prepared fi-oxoesters. The stepwise growing chain is picked up by an acyl-carrier protein (ACP). 

A -protected penultimate amino acid (3) protocol for introduction of the second and third residues when the sequence poses a risk of serious chain loss due to diketopiperazine (DKP) formation (4) stepwise chain elongation using Fmoc protocols to complete on-resin assembly of the desired C-terminal-modified peptide and (5) acidolytic cleavage to release the peptide into solution. 

Preparation of the C-terminal allyl ester protected peptide-resin is carried out by careful introduction of the second and third residues using protocols to minimize DKP formation followed by standard stepwise chain elongation as outlined in Subheadings 3.1.3. and 3.1.4., respectively. 

The side-chain protection of Asp and Glu is essential in peptide-chain elongation steps with these residues or when present as C-termini in segments that are used as carboxy components. The only known way to introduce unprotected Asp and Glu residues in stepwise elongation steps is through their V-carboxyanhy-drides.[ l Protonation of the guanidino group is sufficient in most cases of peptide synthesis in solution. 

Synthesis of large peptides by stepwise chain elongation on a polymeric support. 

The correctly positioned eukaryotic SOS ribosome-Met-tRNAj complex is now ready to begin the task of stepwise addition of amino acids by the in-frame translation of the mRNA. As is the case with initiation, a set of special proteins, termed elongation factors (EFs), are required to carry out this process of chain elongation. The key steps in elongation are entry of each succeeding aminoacyl-tRNA, formation of a peptide bond, and the movement, or translocation, of the ribosome one codon at a time along the mRNA. 

Chessari, S. Thomas, R. Polticelli, F. Luisi, P. L., The production of de novo folded proteins by a stepwise chain elongation A model for prebiotic chemical evolution of macromolecular sequences. Chemistry Biodiversity 2006, 5, 1202-1210. 

In addition to normal chain elongation in the C -> N direction, solid-phase segment coupling has been carried out by N C elongation [140-144]. For stepwise SPPS N —> C chain elongation suffers from the disadvantage that the risks of epimerization of the C-terminus of the resin-bound peptide... 

C-terminal thioester peptides can be prepared in a straightforward manner by using Boc-SPPS [76, 77]. The thioester group is typically an integral component of the resin linker and stepwise chain elongation is conducted under in situ neutralization conditions developed by Kent et al. to ensure the efficiency of couplings... 

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