title: Use of model peptide reactions for the characterization of kinetically controlled ligation.
abstract: Since the introduction of kinetically controlled ligation (KCL), a chemoselective reaction between a peptide-(α)thioarylester and a Cys-peptide-(α)thioalkylester, KCL has been utilized for the total chemical synthesis of large proteins (i.e., lysozyme and HIV-protease) by providing fully convergent synthetic routes. Although KCL has the potential to become an important chemistry for protein synthesis, the principle of KCL is not fully characterized. In particular, prior work on KCL has focused on the reactivity difference of the two different -(α)thioester forms-alkyl vs aryl. Another equally important feature of KCL, Xaa-Cys ligation sites, has not been investigated. The work reported here describes combinatorial KCL reactions using model peptides to dissect the interplay of the Xaa(1), Xaa(2), -(α)thioarylester, and -(α)thioalkylester. Results from these studies provide fundamental insights into the KCL reaction, and will lead to the optimal synthetic route for the routine chemical synthesis of large target protein molecules.
authors: Department of Chemistry, Yonsei University, Shinchon 134 Seoul 120-749 Korea.
authors: Joongoo
authors: J
authors: Lee
authors: Yoonjin
authors: Y
authors: Kwon
authors: Brad L
authors: BL
authors: Pentelute
authors: Duhee
authors: D
authors: Bang
mesh_terms: D020650:Combinatorial Chemistry Techniques; D004951:Esterification; D016333:HIV Protease / Q000138:chemical synthesis; D007700:Kinetics; D008722:Methods; D009113:Muramidase / Q000138:chemical synthesis; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000138:chemical synthesis*
chemical_list: D010455:Peptides; D011506:Proteins; D009113:Muramidase; D016333:HIV Protease