Fragment condensation in peptide

Simplicity. The simplest building blocks suitable for the given task can be efficiently condensed within themselves or with related building units with complementary functionalities, leading to complex structures, analogous to fragment condensation in peptide synthesis . ... 

Fragmentation in mass spectrometry, 529-530 Fragment condensation in peptide synthesis, 1080... 

Fragment condensation of peptides corresponds to a reverse protease reaction -peptide synthesis instead of cleavage - and this is well known in the hterature as well. In fact, proteases have been used extensively for peptide coupling (Jakubke etal, 1985 1996 Jakubke, 1987 1995 Luisi etal, 1977b). This work has shown that even small proteins can be synthesized by block-wise enzymatic couphng (see also Kullmann, 1987, and, for some more recent developments, Celovsky and Bordusa, 2000). 

Let us see where this scheme may bring us, and for this purpose refer to Figure 4.7. This shows a small library of oligopeptides, where one (or more) of these products, indicated in the figure with an asterisk, is endowed with peptidase activity. These peptides then, under the reaction conditions, can catalyze fragment condensation in a specific way - for example of those peptides with a terminal aromatic residue. Following the first condensation step, the catalytic center is inserted into a longer polypeptide, with retention of the catalytic activity. 

Elongation of the peptide bearing a reduced bond can be performed stepwise or by fragment condensation. In the latter case, the carbonyl of the amino acid involved in the reduced peptide bond can be activated (Scheme 1) as no racemization by the oxazol-5(4//)-one mechanism can occur. 

The template was synthesized by classical fragment condensation in solution 39114 (see Section 13.1.1.1). Briefly, the condensation of two peptide intermediates, Fmoc-A2bu(COCH2ONHAloc)-Lys(Boc)-OH and NH2-A2bu(COCH2ONHBoc)-Pro-Gly-OMe, afforded the pentapeptide Fmoc-A2bu-... 

Machauer, R. Waldmann, H. Synthesis of lipi-dated eNOS peptides by combining enzymatic, noble metal- and acid-mediated protecting group techniques with solid phase peptide synthesis and fragment condensation in solution. Chemistry... 

Furthermore, phenyl ester are also suitable substrate mimetics for chymotrypsin-catalyzed peptide synthesis, as was established by Bordusa s group and will demonstrated by sophisticated fragment condensations in Sect. 12.5.3.7. 

Peptide chain built by fragment condensation in solution. 

The N-to-C assembly of the peptide chain is unfavorable for the chemical synthesis of peptides on solid supports. This strategy can be dismissed already for the single reason that repeated activation of the carboxyl ends on the growing peptide chain would lead to a much higher percentage of racemization. Several other more practical disadvantages also tend to disfavor this approach, and acid activation on the polymer support is usually only used in one-step fragment condensations (p. 241). 

An alternative to the synthesis of proteins by classical fragment synthesis in solution or by solid-phase synthesis on a support is the use of enzyme-catalyzed condensation of amino acids or peptides. This possibility was first demonstrated in 1938 91 with the synthesis of poorly soluble benzoyl-leucyl-leucine anilide by papain catalysis. After many years, this approach was extended to the preparation of peptide hormones such as Leu-enkephalin 92 and dynorphin(l -8).[93 This was made possible by the use of highly purified enzymes and by careful control of reaction conditions. The basic principles of protease-catalyzed peptide bond formation have been discussed.194 ... 

Route A utilizes Boc/Bzl chemistry for the synthesis of the main peptide with Fmoc/OFm at the side-chain functions where additional chemistry is performed. For synthesis of extended cyclic peptides, the /V "-Fmoc group is removed and the extension is synthesized with Fmoc/ Bzl chemistry, whereas for reverse-extended cyclic peptides, the to-Fm ester is hydrolyzed and the peptide spacer is built up in the N-to-C direction with fluorenylmethyl esters with all the risk of epimerization or more correctly, it is incorporated by fragment condensation. 

Note that proteins are now synthesized routinely by stepwise assembly or fragment condensation (see Vol. E22a, Section 4.1 ) 67 68 and chances of product contamination with shorter fragments that may have similar retention times under RP-HPLC should be considered 69 Additionally, size-exclusion HPLC was found to be particularly useful in distinguishing linear from cyclic peptides. 

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