Phenylglycine racemization in Fmoc-based solid-phase peptide synthesis

• Verfasst von: Liang, Chen [VerfasserIn]
• Verfasst von: Behnam, Mira A. M. [VerfasserIn]
• Verfasst von: Sundermann, Tom R. [VerfasserIn]
• Verfasst von: Klein, Christian D. [VerfasserIn]
• Titel: Phenylglycine racemization in Fmoc-based solid-phase peptide synthesis
• Titelzusatz: stereochemical stability is achieved by choice of reaction conditions
• Verf.angabe: Chen Liang, Mira A.M. Behnam, Tom R. Sundermann, Christian D. Klein
• E-Jahr: 2017
• Jahr: 21 April 2017
• Umfang: 5 S.
• Fussnoten: Gesehen am 18.09.2018
• Titel Quelle: Enthalten in: Tetrahedron letters
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1959
• Jahr Quelle: 2017
• Band/Heft Quelle: 58(2017), 24, Seite 2325-2329
• ISSN Quelle: 1873-3581
• DOI: doi:10.1016/j.tetlet.2017.04.047
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Epimerization
• Sach-SW: Peptides
• Sach-SW: Phenylglycine
• Sach-SW: Racemization
• Sach-SW: Solid-phase peptide synthesis
• Sach-SW: Stability
• K10plus-PPN: 1581074395

Abstract

Phenylglycine-containing peptides have broad applications in medicinal chemistry, but their synthetic accessibility is complicated by the risk of epimerization during solid-phase peptide synthesis (SPPS). Phenylglycine is therefore often considered a troublesome residue. This work studies the extent of Phg racemization under different Fmoc-SPPS reaction conditions. It is shown that the base-catalyzed coupling of Fmoc-Phg is the critical step for racemization. However, racemization can be reduced to a negligible level if DEPBT or COMU combined with TMP or DMP are employed during this step. Resin-bound peptides are remarkably resistant against epimerization during extended incubation under basic conditions and the free peptides were stable in buffer solutions used for biological assays.