title: Understanding acid lability of cysteine protecting groups.
abstract: Cys-disulfide bonds contribute to the stabilization of peptide and protein structures. The synthesis of these molecules requires a proper protection of Cys residues, which is crucial to prevent side-reactions and also to achieve the correct Cys connectivity. Here we undertook a mechanistic study of a set of well-known acid-labile Cys protecting groups, as well other new promising groups, in order to better understand the nature of their acid-lability. The stability of the carbocation generated during the acid treatment was found to have a direct impact on the removal of the protective groups from the corresponding protected Cys-containing peptides. Hence a combination of steric and conjugative effects determines the stability of the carbocations generated. Here we propose diphenylmethyl (Dpm) as a promising protecting group on the basis of its intermediate relative carbocation stability. All the optimized geometries and energies presented in this study were determined using a B3LYP/6-31G(d,p) calculation. The results discussed herein may be of broader applicability for the development of new protecting groups.
authors: Institute for Research in Biomedicine-IRB Barcelona, Baldiri Reixac 10, 08028-Barcelona, Spain.
authors: Iván
authors: I
authors: Ramos-Tomillero
authors: Lorena
authors: L
authors: Mendive-Tapia
authors: Miriam
authors: M
authors: Góngora-Benítez
authors: Ernesto
authors: E
authors: Nicolás
authors: Judit
authors: J
authors: Tulla-Puche
authors: Fernando
authors: F
authors: Albericio
mesh_terms: D003545:Cysteine / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D010455:Peptides; D003545:Cysteine
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