Backbone Amide Linker (BAL) Strategy for Nα-9-Fluorenylmethoxycarbonyl (Fmoc) Solid-Phase Synthesis of Unprotected Peptide p-Nitroanilides and Thioesters

Jordi Alsina, T. Scott Yokum, Fernando Albericio, George Barany

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

A novel and general backbone amide linker (BAL) strategy has been devised for preparation of C-terminal modified peptides containing hindered, unreactive, and/or sensitive moieties, in concert with Nα-9-fluorenylmethoxycarbonyl (Fmoc) solid-phase synthesis protocols. This strategy comprises (i) start of peptide synthesis by anchoring the penultimate residue, with its carboxyl group orthogonally protected, through the backbone nitrogen, (ii) continuation with standard protocols for peptide chain elongation in the C → N direction, (iii) selective orthogonal removal of the carboxyl protecting group, (iv) solid-phase activation of the pendant carboxyl and coupling with the desired C-terminal residue, and (v) final cleavage/deprotection to release the free peptide product into solution. To illustrate this approach, several model peptide p-nitroanilides and thioesters have been prepared in excellent yields and purities, with minimal racemization. Such compounds are very difficult to prepare by standard Fmoc chemistry, including the BAL strategy as originally envisaged.

Original languageEnglish (US)
JournalJournal of Organic Chemistry
Volume64
Issue number24
StatePublished - Nov 26 1999

Fingerprint Dive into the research topics of 'Backbone Amide Linker (BAL) Strategy for Nα-9-Fluorenylmethoxycarbonyl (Fmoc) Solid-Phase Synthesis of Unprotected Peptide p-Nitroanilides and Thioesters'. Together they form a unique fingerprint.

Cite this