Protected peptide fragments condensation

Synthesis of the peptide Ac-A-Bn-C-OH was performed by a stepwise solid-phase fragment condensation approach, as shown in Scheme 3, using the general procedures of the automated solid-phase method. The synthesis began with Boc-C-resin support and continued with the stepwise addition of protected peptide fragments until the completed peptide was assembled on the resin. The supported peptide Ac-A-Bn-C-resin was obtained after deprotection of Boc-A-Bn-C-resin and acetylation of the free amino groups. 

Fig. l The use of the 2-chlorotrityl chloride resin for the preparation of protected peptides and proteins. Either amino acids (a) or fully protected peptide fragments (b) are condensed to the growing peptide chain on the resin. 

Scheme 14 General Course of the Combined Solid-Phase Peptide Synthesis Substrate Mimetic Fragment Condensation Approach Generation of the Protected Peptide Fragment by Aminolysis Using an Amino Acid Substrate Mimetic, and Irreversible Protease-Catalyzed Fragment Condensation ...

In general, protected peptide fragments of any length can be used in the condensation reaction, if they are of satisfactory purity and solubility. Usually, fragments of up to 15 amino acids in length are used, because of their simpler pinification by RP-HPLC compared with the longer peptides. The solubility of protected peptide acids is independent of their length. 

It has long been recognized that fragment condensation on a solid phase would be highly desirable. 1,5,6 However, the solid-phase fragment coupling approach has been limited by the notoriously poor solubility properties of fully protected peptides that make them difficult to purify and characterize. 

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