Microwave-assisted cleavage of Alloc and Allyl Ester protecting groups in solid phase peptide synthesis

Abstract

Orthogonal protection of amino acid side chains in solid phase peptide synthesis allows for selective deprotection of side chains and the formation of cyclic peptides on resin. Cyclizations are useful as they may improve the activity of the peptide or improve the metabolic stability of peptides in vivo. One cyclization method often used is the formation of a lactam bridge between an amine and a carboxylic acid. It is desirable to perform the cyclization on resin as opposed to in solution to avoid unwanted side reactions; therefore, a common strategy is to use -Alloc and -OAllyl protecting groups as they are compatible with Fmoc solid phase peptide synthesis conditions. Alloc and -OAllyl may be removed using Pd(PPh ) and phenylsilane in DMF. This method can be problematic as the reaction is most often performed at room temperature under argon gas. It is not usually done at higher temperatures because of the fear of poisoning the palladium catalyst. As a result, the reaction is long and reagent-intensive. Herein, we report the development of a method in which the -Alloc/-OAllyl groups are removed using a microwave synthesizer under atmospheric conditions. The reaction is much faster, allowing for the removal of the protecting groups before the catalyst is oxidized, as well as being less reagent-intensive. This method of deprotection was tested using a variety of amino acid sequences and side chain protecting groups, and it was found that after two 5-min deprotections at 38°C, all -Alloc and -OAllyl groups were removed with >98% purity. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Optimized Methods for the Production and Bioconjugation of Site-Specific, Alkyne-Modified Glucagon-like Peptide-1 (GLP-1) Analogs to Azide-Modified Delivery Platforms Using Copper-Catalyzed Alkyne–Azide Cycloaddition

“…Thus, as Fmoc-Lys­(ivDde)-OH is expensive and required long deprotection times, Fmoc-Lys­(Alloc)-OH, which is inexpensive compared to Fmoc-Lys­(ivDde)-OH but requires expensive and toxic reagents for Alloc deprotection, was also assessed ( 20 , Scheme ). Following Alloc deprotection, using tetrakis­(triphenyl­phosphine)­palladium(0) and phenylsilane, propiolic acid was incorporated using EEDQ to yield G26A3 ( 23 ; 9.5% yield; Figures and S3). Overall, each alkyne-modified GLP-1 analog was obtained in ≥96% purity in yields between 9.5% and 25% (Figure ).…”

WS2 and MoS2 biosensing platforms using peptides as probe biomolecules

“…Peptides POG (with amino acid sequence G(POG) 10 ) and FAM-PRG (with amino acid sequence 5-FAM-G(PRGPOG) 5 ; FAM, 5-Carboxyfluorescein) were synthesized by Chinese Peptide Company (Hangzhou, China). Other peptides FAM-5G (with amino acid sequence FAM-GGGGG), FAM-5R (with amino acid sequence FAM-RRRRR), FAM-POG (with amino acid sequence FAM-G(POG) 10 ) were synthesized in-house by standard Fmoc solid phase synthesis method 41 . Briefly, the peptides were synthesized on 2-chlorotrityl chloride resin at a 0.1 mmol scale.…”

Chemical synthesis of site-selective advanced glycation end products in α-synuclein and its fragments

“…The Alloc-group was effectively and selectively removed by treatment with a palladium catalyst and phenylsilane. 33 Then, the free primary amino groups in the Lys side-chains were glycated by reductive amination with the protected carbonyl components (aldehyde or ketone, respectively). This two-step procedure inspired by Pels et al follows the natural mechanism of the reductive amination reaction.…”