Solid-phase peptide synthesis control

Memfield successfully automated all the steps m solid phase peptide synthesis and computer controlled equipment is now commercially available to perform this synthesis Using an early version of his peptide synthesizer m collaboration with coworker Bemd Gutte Memfield reported the synthesis of the enzyme ribonuclease m 1969 It took them only SIX weeks to perform the 369 reactions and 11 391 steps necessary to assemble the sequence of 124 ammo acids of ribonuclease... 

Without doubt, the solid-phase peptide synthesis (Merrifield method) remains a preferred method for controlling all five critical molecular design parameters (size, shape, topology, flexibility, and surface chemistry) by precisely producing amino-acid sequences in a stepwise fashion. The scope and limitations of this approach have been reviewed [34] and widely recognized [35]. These solid-phase syntheses with protection/deprotection procedures are used routinely to produce numerous, previously unattainable [36], polypeptides and polynucleotides. One of the ultimate synthetic efforts in the control of CMDPs was the total synthesis by Khorana et al. [37] of a DNA molecule in the 1960s. 

Acetaldehyde/chloranil test, a monitoring method for the control of complete coupling reaction in solid-phase peptide synthesis [T. Voikovsky, Peptide Res. 1995, 8, 236]. 

This work has reported on a chemically well defined class of graft polymer resin supports combining the mechanical stability of a hydrophobic cross-linked PS matrix with the beneficial features of readily solvatable polar PEG chains. These PEG-PS supports show excellent physicochemical properties and are demonstrably useful for solid-phase peptide synthesis. The PEG/PS ratio can be controlled readily on the basis of the level of PS functionalization and/or the molecular weight of heterobifunctional PEG used. The PEG-PS supports prepared as described... 

M. Horn, C. Novak, A monitoring and control chemistry for solid-phase peptide synthesis, Amer. Biotech. Lab. 5 12-16 (1987)... 

Can an imprinted surface be synthesized in a step-wise fashion, in a manner analogous to solid phase peptide synthesis, such that each functional building brick of the imprint site is positioned in exactly the right place for the chemical task (e.g., binding, catalysis, controlled release) it is designed to do ... 

Solid phase peptide synthesis is the only widely practiced technique of facilitation but several other methods have also been proposed for the rapid construction of long peptide chains. Some of these alternative approaches have certain advantages over solid phase synthesis reactions carried out in solution are not affected by the rate-limiting control of the gel. Also, where isolation of intermediates is possible, these can be analyzed and purified. A major disadvantage, however, common to the various techniques discussed below, is that they are less conducive to mechanization and automation than the Merrifield method. 

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