Active oligopeptide fragments

The use of SPPS allows synthesis of both native oligopeptides and important synthetic analogues. Many of these fragments or substituted analogues have been found to be equal to, or more potent than, the parent molecule and to exhibit long-acting and antagonistic activities. 

Another solid phase fragment condensation with CDI and 1-hydroxybenzotriazole in the synthesis of the human insulin B-chain afforded the oligopeptide in 75% yield. The reaction time with the coupling pair CDI/HOBt was shorter than in the case of the DCC/ HOBt system.136 The CDI/HOBt activation method was also applied to the synthesis of a... 

Steps a and b of this synthetic procedure were performed under standard activation and oxidation conditions. It is advantageous that in the final deprotection step c the trimethylsilylethyl group is cleaved by / -fragmentation by the action of TBAF simultaneously with tert-hutyl protective groups present in the oligopeptide chain. 

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. 

Figure 4.7 Fragment condensation of short, prebiotically formed, oligopeptides. The asterisk indicates the catalytically active peptide, which can induce the fragment condensation by reverse peptide hydrolysis n peptides (e.g., ten residues long) react with each other to build ideally 20-peptides, and of these, m react further (to build ideally 40-peptides, of course in practice all possible mixtures may be present), and m are eliminated because of being unusable (e.g., insoluble) under the contingent conditions - and so on.

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