RESUMO
An efficient methodology for ligation at glutamate (Glu) is described. A γ-thiol-Glu building block was accessed in only three steps from protected glutamic acid and could be incorporated at the N-terminus of peptides. The application of these peptides in one-pot ligation-desulfurization chemistry is demonstrated with a range of peptide thioesters, and the utility of this methodology is highlighted through the synthesis of the osteoporosis peptide drug teriparatide (Forteo).
Assuntos
Ácido Glutâmico/química , Peptídeos/química , Peptídeos/síntese química , Teriparatida/síntese química , Estrutura Molecular , Teriparatida/químicaRESUMO
An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides--ovine-corticoliberin and Forteo--and the human erythrocyte acylphosphatase protein (â¼11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc-solid-phase peptide synthesis.