Chemical Properties
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Uses
Fmoc-Arg(Pbf)-OH is a Fmoc-protected amino acid derivative that can be used to create arginine-containing peptides. The 2,2,4,6,7-pentamethyIdlhydrobenzofuran-5-sulfonyl group (Pbf) can be easily cleaved by trifluoroacetic acid (TFA).
Uses
Fmoc-L-Arg(Pbf)-OH is an amino acid building block used in peptide synthesis. With a growing peptide drug market the fast, reliable synthesis of peptides is of great importance.
Definition
Fmoc-Arg(Pbf)-OH is the standard derivative for the introduction of Arg in Fmoc SPPS. In the preparation of peptides containing both Arg and Trp, it is recommended that this derivative is used in conjunction with Fmoc-Trp(Boc)-OH. The Pbf side-chain protecting group is removed with TFA approximately 1-2 times faster than Pmc. TFA cleavage is best performed in the presence of a silane scavenger. The Pbf group of Fmoc-Arg(Pbf)-OH can be cleaved under moderate acid conditions.
General Description
Fmoc-Arg(Pbf)-OH, which is the most used building block for the introduction of Arg into SPPS, is the most expensive of all protected proteinogenic amino acids currently on the market and, like all Arg derivatives, it undergoes an important side-reaction upon activation. It is a highly problematic amino acid because of its ability to react intramolecularly, leading to its δ-lactam derivative. Arg is the key for the development of the so-called Cell-Penetrating Peptides[1].
Reactivity Profile
The Pbf group of Fmoc-L-Arg(Pbf)-OH can be cleaved under moderate acid conditions. The amount of tryptophan alkylation is significantly reduced compared to other arginine side chain protecting groups, especially in the absence of scavengers. In one example reported in the literature, a peptide containing Arg(Pmc) was cleaved, and deprotected TFA resulted in 46% of the desired peptide.
reaction suitability
reaction type: Fmoc solid-phase peptide synthesis
Synthesis
The synthesis method of Fmoc-L-Arg(Pbf)-OH: first esterifies the carboxyl group of arginine, then introduces a Boc group on the amino group to protect the amino group, introduces a Pbf group on the guanidine group, and removes the Boc group , saponification, and finally the introduction of the Fmoc group on the amino group.
Solubility in organics
≥64.9 mg/mL in DMSO; insoluble in H2O; ≥2.14 mg/mL in EtOH with ultrasonic
References
[1] Torre B, et al. Successful Development of a Method for the Incorporation of Fmoc-Arg(Pbf)-OH in Solid-Phase Peptide Synthesis using N Butylpyrrolidinone (NBP) as Solvent. Green Chemistry, 2020; 22: 3162-3169.
