Handles for Fmoc Solid-Phase Synthesis of Protected Peptides

Abstract

Protected peptide fragments are valuable building blocks for the assembly of large peptide sequences through fragment condensation approaches, whereas protected peptides are typically synthesized for the preparation of amide-bridge cyclic peptides in solution. Efficient synthesis of both protected peptides and protected peptide fragments by solid-phase peptide synthesis methodology requires handles that attach the growing peptides to the polymeric support and can be cleaved under appropriate conditions, while maintaining intact the side-chain protecting groups. Here, we provide an overview of attachment methods described in the literature for the preparation of protected peptides using Fmoc/tBu chemistry, including the most commonly used acid-labile linkers along with the most recent and sophisticated.

Determining the Secondary Structure of Membrane Proteins and Peptides Via Electron Spin Echo Envelope Modulation (ESEEM) Spectroscopy

“…The peptides were cleaved, deprotected, and isolated from their resin support in an acidic environment. The cleavage and deprotection cocktail was designed and optimized according to the sequence, length, and protection groups used on the amino acid side chain (Góngora-Benítez, Tulla-Puche, & Albericio, 2013; Mäde, Els-Heindl, & Beck-Sickinger, 2014). Most cocktails are TFA-based and the amino acid composition of the peptide dictates the final concentration of TFA, type of scavengers used, and reaction times.…”

An efficient solid-phase strategy for total synthesis of naturally occurring amphiphilic marine siderophores: amphibactin-T and moanachelin ala-B

“…35,36 To optimize the debenzoylation process, the resin was divided into two equal portions; first portion of resin was treated with 25% NH 3 (2 × 30 min) and subjected for HPLC purity. Peptide with the sequence of DA-Lys-Ser-Orn(OH,Ac)-OH was prepared on 2-CTC resin (83 mg, 0.05 mmol, 0.6 mmol g −1 ) under standard Fmoc-chemistry protocols (Scheme 2).…”

Untapped Opportunities of Resin‐to‐Resin Transfer Reactions (RRTR) for the Convergent Assembly of Multivalent Peptide Conjugates

“…The TentaGel‐based resins ensure sufficient swelling in NMP ( N ‐methyl‐2‐pyrrolidone) for penetration of the (protected) oligopeptides. Our choice for the safety‐catch donor resin allows for the standard use of automated Fmoc/ t Bu SPPS (solid‐phase peptide synthesis) procedures to generate sequences . Inconsistencies from this resin are known, and we relied on a Gly‐precoupled version to eliminate concerns with loading yields, overacylation, and epimerization.…”

“…Our choice for the safety-catch donor resin allows for the standardu se of automated Fmoc/tBu SPPS (solid-phase peptides ynthesis) procedures to generate sequences. [59][60][61] Inconsistencies from this resin are known,a nd we relied on aG ly-precoupled version to eliminate concerns with loading yields, overacylation, and epimerization.P rior to addition to the RRTR mixture, the sulfonamide moiety was activated by typical N-alkylation with iodoacetonitrile. [62] After peptider elease, the relative inertness of the reacted linker avoids interference with subsequent steps, verification by color testing, monitoring through photolysis (365 nm) or isolation of the completed conjugate.…”