TY - JOUR

T1 - Microwave heating in solid-phase peptide synthesis

AU - Pedersen, Søren Ljungberg

AU - Shelton, Anne Pernille Tofteng

AU - Malik, Leila

AU - Jensen, Knud Jørgen

N1 - This journal is © The Royal Society of Chemistry 2012

PY - 2012

Y1 - 2012

N2 - 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(a)-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 ß-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 ß-peptides, peptoids and pseudopeptides are also evaluated in this critical review (254 references).

AB - 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(a)-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 ß-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 ß-peptides, peptoids and pseudopeptides are also evaluated in this critical review (254 references).

KW - Glycopeptides

KW - Microwaves

KW - Peptides

KW - Peptoids

KW - Phosphopeptides

KW - Solid-Phase Synthesis Techniques

U2 - 10.1039/c1cs15214a

DO - 10.1039/c1cs15214a

M3 - Journal article

C2 - 22012213

VL - 41

SP - 1826

EP - 1844

JO - Chemical Society Reviews

JF - Chemical Society Reviews

SN - 0306-0012

IS - 5

ER -