Microwave-assisted solid-phase peptide synthesis

A recent development in this context is the Liberty system introduced by CEM in 2004 (see Fig. 3.25). This instrument is an automated microwave peptide synthesizer, equipped with special vessels, applicable for the unattended synthesis of up to 12 peptides employing 25 different amino acids. This tool offers the first commercially available dedicated reaction vessels for carrying out microwave-assisted solid-phase peptide synthesis. At the time of writing, no published work accomplished with this instrument was available. 

Erdelyi M, Gogoll A (2002) Rapid Microwave-Assisted Solid Phase Peptide Synthesis. Synthesis 1592-1596... 

Erdelyi, M. and Gogoll, A., Rapid microwave-assisted solid phase peptide synthesis, Synthesis, 2002, 1592-1596. 

Aral, J. Tagari, P. Holder, R. Long, J. Diamond, S. Miranda, L. Effects of Coupling Reagent, Base, and Solvent Choice on Microwave-Assisted Solid-phase peptide synthesis presented at 3rd International Micro-wave Conference, Orlando, EL, 2005. 

P-Amino acid oligomers (P-peptides) present a unique class of peptides. In contrast to their natural a-amino acid counterparts, P-peptides require relatively few residues to form secondary structures like turns, helices, or sheets (Seebach et al. 1996, 2001, 2004 Cheng et al. 2001). However, these secondary structures can also severely hamper the synthesis of these compounds (Murray and Gellman 2005 Lelais et al. 2006). To increase the synthetic efficiency of helical P-peptides, microwave-assisted solid phase peptide synthesis (SPPS) protocols have also been applied (Murray and Gellman 2005 Lelais et al. 2006 Erddlyi and Gogoll 2002). 

Harris P, Williams G, Shepherd P, Brimble M (2008) The synthesis of phosphopeptides using microwave-assisted solid phase peptide synthesis. Int J Pept Res Ther 14 387-392... 

Coantic S, Subra G, Martinez J (2008) Microwave-assisted solid phase peptide synthesis on high loaded resins. Int J Pept Res Ther 14 143-147... 

Microwave-Assisted Solid-Phase Peptide Synthesis... 

One of the cornerstones of combinatorial synthesis has been the development of solid-phase organic synthesis (SPOS) based on the original Merrifield method for peptide preparation [19]. Because transformations on insoluble polymer supports should enable chemical reactions to be driven to completion and enable simple product purification by filtration, combinatorial chemistry has been primarily performed by SPOS [19-23], Nonetheless, solid-phase synthesis has several shortcomings, because of the nature of heterogeneous reaction conditions. Nonlinear kinetic behavior, slow reaction, solvation problems, and degradation of the polymer support, because of the long reactions, are some of the problems typically experienced in SPOS. It is, therefore, not surprising that the first applications of microwave-assisted solid-phase synthesis were reported as early 1992 [24],... 

Carenbauer, A.L. Cecil, M.R. CzERWiNSKi, A. Darlak, K. Dariak, M. Long, D.W. Valenzuela, F. Barany, G. Microwave Assisted Solid Phase Synthesis on CLEAR Supports Presented at the 19th American Peptide Symposium, San Diego, C.A. 

The application of transition metal-mediated reactions on solid support is an area of supreme interest for both peptide chemistry and the synthesis of nonpeptidic drug-like molecules. Although many metal-catalyzed reactions have been carried out on resin-bound scaffolds, there are scarce examples of metal-mediated solid-phase reactions promoted by a complexing agent that is covalently bound with the resin in close proximity of the scaffold. Dai and Sun have recently proposed an ingenious route toward the microwave-assisted solid-phase synthesis of a small library of 2-(hetero)aryl indoles. The authors demonstrated the strategic use of a tailor-made linker that features the dual function of a normal linker for scaffold attachment as well as of a promoter for the Cu(II)-mediated hetero-annulation of the intermediates (Scheme 8.17). 

Key words Microwave-assisted peptide synthesis. Solid-phase peptide synthesis. Difficult peptides. Microwave heating, Alkyne... 

Chi Y, Zhang H, Huang W, Zhou J, Zhou Y, Qian H, Ni S (2008) Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide. Bioorg Med Chem 16 7607-7614... 

The first installment in this series (Volume 267, 1996) mostly covered peptide and peptidomimetic based research with just a few examples of small molecule libraries. In this volume we have compiled cutting-edge research in combinatorial chemistry, including divergent areas such as novel analytical techniques, microwave-assisted synthesis, novel linkers, and synthetic approaches in both solid-phase and polymer-assisted synthesis of peptides, small molecules, and heterocyclic systems, as well as the application of these technologies to optimize molecular properties of scientific and commercial interest. 

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