Microwave-assisted peptide synthesis

Rybka, a. Microwave Assisted Peptide Synthesis CEM International Microwave Conference, 2005, Orlando, FL. 

Parallel microwave-assisted peptide synthesis can be performed in 96-welI polypropylene microtiter filter plates in a multimode microwave instrument like the MARS from CEM [26-28]. The... 

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

The standard conditions used for microwave-assisted peptide synthesis are fairly mild, and our typical protocol for base-labile Fmoc peptide synthesis is deprotection with 20 % piperidine at 75 °C for 3 min and coupling with HBTU and DIEA at 75 °C for 5 min. Due to the temperatures used during microwave-assisted peptide synthesis there is an increased potential for unwanted side reactions. Racemization of the activated amino acid during the coupling step is a known issue even under conventional synthesis conditions and is a problem for Cys and His residues specifically. To investigate this potential problem a model 20-mer peptide that contained each of the naturally occurring amino acids was synthesized under both conventional and microwave conditions [11]. The peptides were hydrolyzed in 6N DCI/D2O, and the resulting free amino acids were subjected to GC-MS analysis to calculate the... 

Microwave-assisted peptide synthesis has become the method of choice for the synthesis of difficult peptides, but it has also been used extensively in academia and industry for the routine synthesis of a variety of different types of peptides [13-16]. Peptides... 

This protocol outlines the general procedure for both manual and automated microwave-assisted peptide synthesis. For the manual synthesis the acyl carrier protein, AGP (65-74) sequence was selected as a representative difficult peptide. The automated synthesis features the preparation of p-amyloid (1 2), another peptide that is known to be difficult to synthesize. Both methods provide the peptides in excellent purity with good yields in a fraction of the time it would take to perform these syntheses using conventional, room temperature synthesis conditions. 

Automated Microwave-Assisted Peptide Synthesis of p-Amyioid (1-42)... 

MicFowave methods for manual microwave-assisted peptide synthesis... 

Manual microwave-assisted peptide synthesis can also be performed in a multimode microwave system [34]. 

Mmray JK, Gellman SH (2005) Microwave-assisted parallel synthesis of a 14-helical p-peptide library. J Comb Chem 8 58-65... 

Equipment Single mode microwave synthesizer configured for manual peptide synthesis equipped with a fiber optic temperature probe (Discover SPS microwave-assisted peptide synthesizer, GEM Corporation) (rrr Note 1). 

Oxazoles have attracted considerable interest due their presence as subunits of several biologically active compoimds or as rigid mimetics of a peptidic ring. A first synthesis of 2-phenyl-4,5-substituted oxazoles 54 [47] was described by microwave-assisted reaction of enolizable ketones with benzoni-trile in the presence of mercury(II) p-toluenesulfonate (Scheme 17). 

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. 

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],... 

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. 

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. 

Click chemistry also found applications in peptides and peptidomimetics. Alkyne-azide cycloaddition between two peptide strands provided an efficient convergent synthesis of triazole ring-based P-tum mimics <07CC3069>. The synthesis of a-substituted prolines has been accomplished by microwave-assisted Huisgen 1,3-dipolar cycloaddition between azides and orthogonally protected a-propynyl proline in the presence of Cu(I) sulfate <07SL2882>. The synthesis of new trifluoromethyl peptidomimetics with a triazole moiety has been reported <07TL8360>. 

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. 

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). 

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