Microwave heating in solid-phase peptide synthesis

Abstract

The highly refined organic chemistry in solid-phase synthesis has made it the method of choice not only to assemble peptides but also small proteins - mainly on a laboratory scale but increasingly also on an industrial scale. While conductive heating occasionally has been applied to peptide synthesis, precise microwave irradiation to heat the reaction mixture during coupling and N(α)-deprotection has become increasingly popular. It has often provided dramatic reductions in synthesis times, accompanied by an increase in the crude peptide purity. Microwave heating has been proven especially relevant for sequences which might form β-sheet type structures and for sterically difficult couplings. The beneficial effect of microwave heating appears so far to be due to the precise nature of this type of heating, rather than a peptide-specific microwave effect. However, microwave heating as such is not a panacea for all difficulties in peptide syntheses and the conditions may need to be adjusted for the incorporation of Cys, His and Asp in peptides, and for the synthesis of, for example, phosphopeptides, glycopeptides, and N-methylated peptides. Here we provide a comprehensive overview of the advances in microwave heating for peptide synthesis, with a focus on systematic studies and general protocols, as well as important applications. The assembly of β-peptides, peptoids and pseudopeptides are also evaluated in this critical review (254 references).

Microwave-Assisted Syntheses of Bioactive Seven-Membered, Macro-Sized Heterocycles and Their Fused Derivatives

“…Compared to conventional SPPS, this methodology results in gains on final peptide yields, especially for peptides with long sequences or peptides including "difficult" sequences (such as β-sheet type structures), combined with an increase of the crude peptide purity [77]. Moreover, the MW-activation is not detrimental in terms of optical purity: the racemization rates are usually very close when heating at the same temperature under MW-activation or when using a conventional heating.…”

New Methods for Chemical Protein Synthesis

“…Since Merrifield invented the technology in 1963, SPPS has become the primary approach for the routine preparation of peptides [28][29][30][31][32]. The general scheme of solid phase peptide synthesis is illustrated in Fig.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…Three, four and five-membered ring systems have been previously reviewed by our group and are not addressed in this issue [17]; the synthesis of seven-membered ring and macrocyclic systems will be reviewed by us shortly. essential oil extraction and biochemical processes [10][11][12][13][14]. In addition, the MW-assisted organic syntheses can also lead in short time to large libraries of small-sized heterocyclic compounds featuring high molecular diversity with potential bioactivities [15,16].…”