Fmoc-hArg(Pbf)-OH is an advanced unnatural amino acid derivative equipped with orthogonal protecting groups, specifically optimized for standard Fmoc solid-phase peptide synthesis (SPSS). By introducing homoarginine (hArg)—which contains one more methylene group than natural arginine—into the peptide sequence, it significantly enhances the proteolytic stability and cellular penetration efficiency of peptide drugs. Its side chain is protected by the industry-standard Pbf group, which is highly labile during trifluoroacetic acid (TFA) cleavage, effectively minimizing side reactions. It is an ideal building block for synthesizing high-purity, complex modified peptides.
Sequenza
Fmoc-hArg(Pbf)-OH
Numero CAS
1159680-21-3
Formula molecolare
C35H42N4O7S
Peso Molecolare
662.80
Chemical & Synthesis Advantages Fmoc-hArg(Pbf)-OH perfectly aligns with modern Fmoc/tBu solid-phase peptide synthesis strategies. In peptide synthesis, the protection and deprotection of the strongly basic guanidino group is a core challenge. The side chain of this product utilizes the Pbf (2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl) protecting group. Compared to traditional Pmc or Mtr groups, Pbf offers overwhelming advantages:
- Rapid Cleavage: During the final TFA cleavage step, the removal rate of Pbf is significantly faster than other sulfonyl protecting groups.
- Suppression of Side Reactions: The rapid deprotection effectively reduces the risk of alkylation side reactions caused by carbocations on the side chains of sensitive amino acids like tryptophan (Trp), thereby substantially improving the purity and yield of the crude peptide.
Frontier Applications in Peptide Drug Discovery As an unnatural amino acid, homoarginine (hArg) has a carbon skeleton that is one methylene longer than natural arginine. In innovative drug design, this minor structural modification yields significant biological benefits:
- Enzymatic Stability: Natural proteases (such as Trypsin) typically recognize and cleave the C-terminus of Arg or Lys specifically. Replacing Arg with the unnatural hArg allows the peptide to effectively evade protease recognition, thereby significantly extending the half-life of peptide drugs in plasma.
- Enhanced Cellular Uptake: In research involving guanidino-rich cell-penetrating peptides (CPPs), the additional spatial flexibility provided by hArg optimizes the binding mode between the guanidino group and heparan sulfate on the cell membrane surface, thus drastically improving the transmembrane delivery efficiency of macromolecular drugs.
COA
HPLC
SM
- Initial Development and Chemical Advantages of the Pbf Protecting Group:
Carpino, l. UN., Shroff, H., Triolo, S. UN., Mansour, E. M., Wenschuh, H., & Albericio, F. (1993). “The 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl group (Pbf) as arginine side chain protectant.” Journal of the American Chemical Society, 115(10), 4397-4398. Verification Source: DOI: 10.1021/ja00063a082
- Standard Protocols for Fmoc SPPS and Pbf Application:
Chan, W. C., & Bianco, P. D. (2000). Fmoc Solid Phase Peptide Synthesis: A Practical Approach. Oxford University Press. (See pages 58-60 for standard applications of arginine derivative side-chain protection). Verification Source: ISBN: 978-0199637249
- Biological Validation of Side-Chain Length (Homoarginine) on Enhancing Cellular Uptake:
Wender, P. UN., Mitchell, D. J., Pattabiraman, K., Pelkey, E. T., Steinman, l., & Rothbard, J. B. (2000). “The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters.” Proceedings of the National Academy of Sciences, 97(24), 13003-13008. Verification Source: DOI: 10.1073/pnas.97.24.13003
