Solid-phase peptide synthesis description

A wide choice of peptide synthesizers is currently available, ranging from manual to fully automated. They are all based on solid-phase peptide synthesis methodologies in which either f-butoxy carbonyl (t-boc) (11), or 9-fluor-enylmethoxycarbonyl (Fmoc) (12) is the major protecting group during synthesis. A detailed description of peptide synthesis is clearly beyond the scope of this chapter, and further information on practical and theoretical approaches to this chemistry may be found elsewhere (13-15). However, a brief outline of solid-phase synthesis may prove useful. 

The patent application as drafted contains a description of how to make the specifically disclosed peptides as well as additional description explaining that it was well within the purview of one of ordinary skill in the art to make hexapep-tide amino acid sequences by standard synthesis, solid phase peptide synthesis or synthesis by recombinant techniques. The patent application also described the in vitro BACE inhibition assay and the data generated from it. The application further explains ... 

In a description of the utility of solid phase peptide synthesis Merrifield made the prophetic observation "A gold mine awaits discovery by organic chemists". Scarely ten years later Leznoff rather ruefully noted "Many gold nuggets have now been mined... and some iron pyrites". We are currently on the crest of what appears to be an ever-increasing wave and we would have to say that the task described by Fettes is certainly impossible. 

Positional scanning, or 1-D indexing, was reported as a deconvolutive technique by Houghten and coworkers [35] and subsequently applied extensively to solid-phase peptide library synthesis. An example of solid-phase small organic molecule 2-D indexed library synthesis and deconvolution was reported by Berk et al. [36]. Description of this strategy, called spatially arrayed mixture (SpAM), and a comparison with classical positional scanning, are shown in Figure 8.9. 

The initial preparation of protein-based polymers utilized solution and solid phase peptide chemistry. This made possible the preparation of more than 1,000 polymer compositions. As discussed in Chapter 5, these compositions were studied for determination of their basic properties, for the development of the set of phenomenological axioms for protein engineering and function, and for the demonstration of the basic mechanism that underlies function. In short, it is the chemical synthesis that has allowed development of much of the basic science and the demonstration of the potential of protein-based materials in a timely manner. Mostly because of the historical relevance, but also because of the unique contributions of chemical synthesis to arriving at satisfactory purification of microbially prepared protein-based polymers, a brief description of the chemical synthesis of protein-based polymers is given below. 

The first description of the total synthesis of the LRF decapeptide was that of Monahan et al.. The peptide had the biological activity of ovine LRF in vivo and in vitro (rats) and caused ovulation in rabbits . Subsequent to that report, several other descriptions of syntheses have appeared which employed classical methods or solid-phase methods . 

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