Native Chemical Ligation is one of the most powerful tools for the preparation of complex peptides and small proteins. However, the classical variant of NCL requires an N-terminal cysteine at the ligation site. Iris Biotech presents an innovative auxiliary reagent for NCL that can be incorporated in place of a glycine residue. Since glycine usually occurs several times in a peptide sequence, this approach significantly increases variability regarding the choice of possible ligation sites. In Native Chemical Ligation, the auxiliary’s SH-group mimics the action of an N-terminal cysteine’s sulfhydryl group.

Following SPPS, the auxiliary is attached to the N-terminus of a peptide sequence in lieu of a glycine residue. The auxiliary’s Fmoc-protected amino functionality can subsequently be deprotected and functionalized, e.g. with a monodisperse PEG. PEGylation is useful for increasing the solubility of peptide fragments, and for facilitating their purification by precipitation with EtOH/Et₂O. These properties are especially valuable if the peptide’s amino acid side chains are supposed to be further derivatized post-SPPS, for example by enzymatic glycosylation. Following NCL, the auxiliary can be conveniently removed by irradiation with UV-light.

→ For convenient peptide thioester formation, Iris Biotech offers innovative Resins and Linkers, such as Hydrazone Resins, SEA Resins and the Dawson Linker

→ Find a huge selection of PEGylation reagents in our Webshop!

• A PEGylated Photocleavable Auxiliary Mediates the Sequential Enzymatic Glycosylation and Native Chemical Ligation of Peptides; C. Bello, S. Wang, L. Meng, K. W. Moremen and C. F. W. Becker; Angewandte Chemie International Edition 2015; 54: 7711-7715. doi:10.1002/anie.201501517