Wydział Chemii

Remigiusz Bąchor

Alicja Kluczyk

Piotr Stefanowicz

Zbigniew Szewczuk

2013

Molecular Diversity

17

605-611

10.1007/s11030-013-9453-y

Naukowa

Angielski

Artykuł

A straightforward cleavage method for Nacylated peptides based on the phenylthiohydantoin (PTH) formation is presented. The procedure could be applied to acid-stable resins, such as TentaGel HL–NH2. We designed a cleavable linker that consists of a lysine residue with the α-amino group blocked by Boc, whereas the ε-amino group is used for peptide synthesis. After the peptide assembly is completed, the protecting groups in peptide side chains are removed using trifluoroacetic acid, thus liberating also the α-amino group of the lysine in the linker. Then the reaction with phenyl isothiocyanate followed by acidolysis causes an efficient peptide release from the resin as a stable PTH derivative. Furthermore, the application of a fixed charge tag in the form of 2-(4-aza-1- azoniabicyclo[2.2.2]octylammonium)acetyl group increases ionization efficiency and reduces the detection limit, allowing ESI-MS/MS sequencing of peptides in the subfemtomolar range. The proposed strategy is compatible with standard conditions during one-bead-one-compound peptide library synthesis. The applicability of the developed strategy in combinatorial chemistry was confirmed using a small training library of α-chymotrypsin substrates.

OBOC, Ionization tag, Quaternary ammonium salts, Peptide cleavage method, Phenylthiohydantoin, Edman degradation

CC-BY

http://dx.doi.org/10.1007/s11030-013-9453-y

http://link.springer.com