Fragment condensation in peptide synthesis

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). 

Benz, H. The Role of Solid-Phase Fragment Condensation (SPFC) in Peptide Synthesis, Synthesis 1994,4, 337. 

R. B. MelTifleld, Solid phase peptide synthesis. I. The synthesis of a tetrapeptide, J. Am. Chem. Soc. 85 2149 (1963) for recent reviews see (a) H. Benz, The role of solid-phase fragment condensation (SPFC) in peptide synthesis, Synthesis p. 337 (1994) (b) P. Lloyd-Williams, F. Alberico, and E. Giralt, Convergent solid phase peptide synthesis. Tetrahedron 49 11065 (1993). 

Carboxylic acid azides give rise to three different reactions under different conditions. Azide coupling (equation 9) was the earliest method in peptide synthesis and is still one of the most important in fragment condensation and preparation of cyclic peptides due to its almost complete lack of racemization. At elevated temperatures a frequent side reaction is the Curtius rearrangement. Trapping of the intermediate isocyanate with amines (equation 10) gives urea derivatives and with carboxylic acids rearranged amides are obtained (equation 11). ... 

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. 

The most successful method of fragment condensation for the synthesis of polypeptides and proteins in solution phase is NCL, reported by Dawson for the first time in 1994 [7]. This was a significant contribution because NCL overcomes one of the main limitations of solid phase peptide synthesis (SPPS), namely the production of long peptide sequences (>50 amino acid residues) [1, 3, 29]. NCL may be used in both solution and solid phases solution phase NCL has been used for the synthesis of small peptides and cyclic peptides [30-32] whereas SPPS is more widely applied in polypeptide and protein synthesis. 

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). 

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. 

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