Nα-Amino acid containing privileged structures: design, synthesis and use in solid-phase peptide synthesis

2018 ◽  
Vol 16 (29) ◽  
pp. 5359-5362 ◽  
Author(s):  
Eva Schütznerová ◽  
Adam Přibylka ◽  
Viktor Krchňák
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Privileged Structures

Fmoc-protected Nα-amino acid containing heterocyclic privileged structures, O-(1-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl)-l-serine and O-((S)-5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl)-l-serine, were synthesized on the solid phase from simple commercially available building blocks under mild conditions.

Caged Phospho-Amino Acid Building Blocks for Solid-Phase Peptide Synthesis

2003 ◽  
Vol 68 (17) ◽  
pp. 6795-6798 ◽  
Author(s):  
Deborah M. Rothman ◽  
M. Eugenio Vazquez ◽  
Elizabeth M. Vogel ◽  
Barbara Imperiali
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks

A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

2019 ◽  
Author(s):  
luis camacho III ◽  
Bryan J. Lampkin ◽  
Brett VanVeller
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Side Chains ◽  
Amino Acid Side Chains ◽  
Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.<br>

scholarly journals Reinvestigation of a Critical Reductive Amination Step Leads to an Optimized Protocol for the Synthesis of N-2-Hydroxybenzylcysteine Peptide Crypto-Thioesters

2020 ◽  
Author(s):  
Skander Abboud ◽  
Vincent AUCAGNE
Keyword(s):  
Peptide Synthesis ◽  
Reaction Mechanisms ◽  
Reductive Amination ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Building Blocks ◽  
Native Chemical Ligation ◽  
Chemical Ligation ◽  
Optimized Protocol ◽  
Depth Study

An in-depth study of the Fmoc-based solid phase peptide synthesis of N-Hnb-Cys crypto-thioester peptides, advantageous building blocks for the native chemical ligation-based synthesis of proteins, led to the identification of epimerized and imidazolidinone side products formed during a key reductive amination step. The understanding of the underlying reaction mechanisms was crucial for the developement of an automatable optimized synthetic protocol.

Instrumentation for automated solid phase peptide synthesis

1999 ◽  
Author(s):  
Linda E. Cammish ◽  
Steven A. Kates
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Reaction Vessel ◽  
Automated System ◽  
Polymeric Support ◽  
Simple Filtration ◽  
Subsequent Activation ◽  
Selection Of

The concept of solid phase peptide synthesis introduced by Merrifield in 1963 involves elongating a peptide chain on a polymeric support via a two-step repetitive process: removal of the Nα-protecting group and coupling of the next incoming amino acid. A second feature of the solid phase technique is that reagents are added in large excesses which can be removed by simple filtration and washing. Since these operations occur in a single reaction vessel, the entire process is amenable to automation. Essential requirements for a fully automatic synthesizer include a set of solvent and reagent reservoirs, as well as a suitable reaction vessel to contain the solid support and enable mixing with solvents and reagents. Additionally, a system is required for selection of specific solvents and reagents with accurate measurement for delivery to and removal from the reaction vessel, and a programmer to facilitate these automatic operations is necessary. The current commercially available instruments offer a variety of features in terms of their scale (15 mg to 5 kg of resin), chemical compatibility with 9-fluorenylmethyloxycarbonyl/tert-butyl (Fmoc/tBu) and tert-butyloxycarbonyl/ benzyl (Boc/Bzl)-based methods, software (reaction monitoring and feedback control), and flexibility (additional washing and multiple activation strategies). In addition, certain instruments are better suited for the synthesis of more complex peptides such as cyclic, phosphorylated, and glycosylated sequences while others possess the ability to assemble a large number of peptide sequences. The selection of an instrument is dependent on the requirements and demands of an individual laboratory. This chapter will describe the features of the currently available systems. As the field of solid phase synthesis evolved, manufacturers designed systems based on the synergy between chemistry and engineering. A key component to an instrument is the handling of amino acids and their subsequent activation to couple to a polymeric support. The goal of an automated system is to duplicate conditions that provide stability to reactive species that might decompose. Standard protocols for automated synthesis incorporate carbodiimide, phosphonium, and aminium/uronium reagents, preformed active esters, and acid fluorides. For further details on coupling methods, see Chapter 3. A second issue related to coupling chemistry is the time required to dissolve an amino acid and store this solution.

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