Hydrophobic Magnetic Nanoparticle Assisted One‐Pot Liquid‐Phase Peptide Synthesis

Abstract

Chemically stable hydrophobic magnetic nanoparticles were prepared by using an isocyanate as an anchoring group and were applied to the soluble tag‐assisted liquid‐phase peptide synthesis of the peptide elastin. Couplings and deprotections were effectively performed in the presence of the nanoparticles, and the desired product was rapidly collected as a “magnetic” precipitate, enabling a one‐pot procedure. Sonication of the nanoparticles significantly suppressed gelation of the reaction mixture, which allowed the highly aggregating elastin peptide to be synthesized in one pot without difficulty.

Total Synthesis of Semaglutide Based on a Soluble Hydrophobic-Support-Assisted Liquid-Phase Synthetic Method

“…Additionally, we also found that the physical properties of the precipitates obtained after almost every coupling or deprotecting reaction were too sticky to be separated from reaction mixtures by vacuum filtration, which caused a decrease in the efficiency of post-synthesis treatment. , In order to solve this technical problem, a magnetic nanoparticle assisted post-synthetic treatment method was put forward by Okada et al In sharp contrast to this, in our study, we found a simple and effective postprocessing method to solve the above problems. Specifically, moderate quantities of diatomite were added to the precipitates in the reaction mixture and well mixed.…”

Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On‐Demand Release

“…Isocyanate ligands, recently reported by Licandro and co‐workers as a new ION functionalization strategy, were chosen for the functionalization of the nanoparticle (NP) surface, where they form carbamates upon reaction with hydroxyl groups on the NP . The advantages of this method include short reaction times, mild reaction conditions, and easy access to ligands with a variety of functional groups.…”

“…Isocyanate ligands, recently reported by Licandro and co-workers as an ew ION functionalization strategy, [26] were chosen for the functionalization of the nanoparticle( NP) surface, where they form carbamates upon reactionw ith hydroxyl groups on the NP. [27] The advantages of this methodi ncludes hort reaction times,m ild reaction conditions, and easy access to ligands with av ariety of functional groups. Maleimide isocyanate 1 (Scheme 1) was synthesized through ap rocedure reported in the literature in five steps with an overall yield of 35 %; [28] all intermediates were obtained without the need for chromatographic purification.…”

Liquid-Phase Peptide Synthesis (LPPS): A Third Wave for the Preparation of Peptides

“…A longer aliphatic chain confers hydrophobicity to the molecule (regardless of the growing peptide chain), which can be precipitated using polar solvents like ACN or MeOH after coupling and Fmoc removal. Tamiaki and co-workers first demonstrated the application of long aliphatic chain substituted alkoxy benzyl alcohol for the synthesis of peptides using Fmoc chemistry (PC1). , Chiba and co-workers further developed this concept using different long aliphatic alkoxy substituents (PolyCarbon) to confer differentiated properties to the growing peptide chains, allowing the isolation of the desired product via precipitation/extraction (PC1–8). − PC1–5 are alkoxybenzyl alcohols for the preparation of C-terminal carboxylic acids; − ,− ,,,− PC6 contains a kind of Rink linker for the preparation of C-terminal amides; PC7 allows the preparation of C-terminal N -ethyl amides; and PC8 allows backbone anchoring through the first amide bond of the peptide. , JITSUBO and BACHEM AG called this technology “molecular hiving” − for peptide synthesis using the LPPS strategy (PC1, PC3, and PC4). − ,, In addition, Ajinomoto developed the so-called Ajiphase protocol, − with a parallel chemistry for the preparation of C-terminal acid and amide peptides with a mimic of trityl group PC9 , and of Rink linker PC10, respe...…”