| Synonym: | N-α-Fmoc-N-ε-t-Boc-L-lysine |
| CAS #: | 71989-26-9 |
| Molecular Formula: | C26H32N2O6 |
| Molecular Weight: | 468.5 |
| Fmoc-Lys(Boc)-OH is a protected derivative of the amino acid lysine, widely used in solid-phase peptide synthesis (SPPS), particularly in Fmoc (fluorenylmethyloxycarbonyl) chemistry. It is essential for incorporating lysine into peptide sequences while protecting its side chain during synthesis. Below is a detailed review of this compound, including its properties, applications, and considerations: Fmoc-Lys(Boc)-OH is a building block for peptide synthesis, designed to incorporate lysine into peptide sequences while protecting its ε-amino side chain with the Boc (tert-butoxycarbonyl) group. This ensures that the side chain remains inert during synthesis and can be deprotected under acidic conditions. 1. Chemical Structure (1). Fmoc Group: The Fmoc (fluorenylmethyloxycarbonyl) group protects the α-amino group of lysine during synthesis. It is removed under basic conditions (e.g., piperidine). (2). Boc Group: The Boc (tert-butoxycarbonyl) group protects the ε-amino side chain of lysine. It is removed under acidic conditions (e.g., trifluoroacetic acid, TFA). (3). Lysine Backbone: The compound includes the lysine amino acid core, with a carboxylic acid group for coupling to the growing peptide chain. 2. Properties (1). Solubility: Fmoc-Lys(Boc)-OH is soluble in polar organic solvents such as DMF (dimethylformamide) and DMSO (dimethyl sulfoxide), making it suitable for SPPS. (2). Stability: The Fmoc group is stable under acidic conditions but can be removed under basic conditions. The Boc group is stable under basic conditions but is cleaved under acidic conditions, typically during the final deprotection step. 3. Applications (1). Peptide Synthesis: Fmoc-Lys(Boc)-OH is used to incorporate lysine into peptide sequences during Fmoc-based SPPS. Lysine is a common amino acid in peptides due to its positive charge and role in protein-protein interactions. (2). Therapeutic Peptides: Lysine-containing peptides are often used in drug development, particularly for antimicrobial peptides and peptide-based vaccines. Fmoc-Lys(Boc)-OH ensures the correct incorporation of lysine without side reactions. (3). Bioconjugation: The deprotected lysine side chain can be used for site-specific bioconjugation, such as attaching fluorescent dyes, biotin, or PEG chains. (4). Branched Peptides: Fmoc-Lys(Boc)-OH is often used in the synthesis of branched or multivalent peptides, where the ε-amino group of lysine serves as a branching point. 4. Advantages (1). Efficient Protection: The Boc group effectively protects the ε-amino side chain, preventing side reactions and ensuring high yields during peptide synthesis. (2). Compatibility: Fmoc-Lys(Boc)-OH is compatible with standard Fmoc-SPPS protocols, including automated synthesizers. (3). Selective Deprotection: The Boc group can be selectively removed during the final cleavage step without affecting other protecting groups that may be present in the peptide. 5. Limitations (1). Deprotection Conditions: The Boc group requires strong acids (e.g., TFA) for removal, which may not be compatible with acid-sensitive peptides or functional groups. (2). Steric Hindrance: The bulky Boc group can sometimes cause steric hindrance during coupling reactions, particularly in sequences with multiple lysine residues. 6. Recent Advancements (1). Improved Coupling: Microwave-assisted SPPS enhances Fmoc-Lys(Boc)-OH incorporation, reducing reaction times and improving yields in lysine-rich peptides. (2). Green Chemistry: Alternatives to DMF (e.g., 2-MeTHF) and reduced TFA volumes in cleavage cocktails improve environmental impact. (3). Automation: Automated synthesizers (e.g., Liberty Blue) optimize Fmoc-Lys(Boc)-OH handling, ensuring reproducibility. (4). Custom Derivatives: Variants like Fmoc-D-Lys(Boc)-OH expand applications to D-amino acid peptides for enhanced stability. (5).Bioconjugation Advances: Post-deprotection ε-amino groups are increasingly used in click chemistry (e.g., azide-alkyne cycloaddition) for precise conjugate synthesis. 7. Comparison with Other Lysine Derivatives (1). Fmoc-Lys(Mtt)-OH: Uses the Mtt (4-methyltrityl) group for side chain protection, which can be selectively removed under mild acidic conditions. (2). Fmoc-Lys(Alloc)-OH: Uses the Alloc (allyloxycarbonyl) group, which can be removed under neutral conditions using palladium catalysts. (3). Fmoc-Lys(Dde)-OH: Uses the Dde (1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) group, which can be removed with hydrazine. Among these, Fmoc-Lys(Boc)-OH is the most widely used due to its balance of stability, ease of deprotection, and compatibility with SPPS. Fmoc-Lys(Boc)-OH is a critical reagent for incorporating lysine into peptides during Fmoc-based SPPS. Its effective protection of the ε-amino side chain, compatibility with standard protocols, and high purity make it a preferred choice for peptide synthesis. However, its steric hindrance, and requirement for strong acid deprotection should be considered when planning experiments. Overall, Fmoc-Lys(Boc)-OH is an indispensable tool for synthesizing lysine-containing peptides in both research and therapeutic applications. References: 1. Peptide Synthesis 2. Overview of Solid Phase Synthesis 3. Fmoc Solid Phase Peptide Synthesis 4. Boc Solid Phase Peptide Synthesis 5. Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences |
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