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Fmoc-His(Trt)-OH Product Information
| Product Name | Fmoc-His(Trt)-OH |
|---|---|
| Synonyms | Nα-Fmoc-Nim-trityl-L-histidine |
| Catalog No. | AS2034 |
| CAS Number | 109425-51-6 |
| Molecular Formula | C40H33N3O4 |
| Molecular Weight | 619.71 g/mol |
| SMILES | OC(=O)C@HNC(=O)OCC5c6ccccc6-c7ccccc57 |
| Storage Temperature | Cool, dry place (≤25°C) |
| Appearance | White powder |
| Specific Rotation | +86° ± 8° (C=5 in CHCl3) |
| Side-Chain Protection | Trt-protected imidazole |
| Primary Application | Fmoc solid-phase peptide synthesis (SPPS) |
Product Overview
Fmoc-His(Trt)-OH is the conventional protected L-histidine building block used in Fmoc-SPPS.
The α-amino group is protected by Fmoc, while the reactive imidazole side chain is protected with trityl (Trt).
Trt protection limits unwanted imidazole chemistry during peptide-chain assembly and can be removed during final acidic cleavage.
Histidine is important in many biological peptides because its imidazole side chain can participate in:
proton transfer
hydrogen bonding
metal coordination
enzyme catalysis
pH-sensitive molecular interactions
Applications in Peptide Synthesis
| Application | Role of Fmoc-His(Trt)-OH |
|---|---|
| Fmoc-SPPS | Standard protected L-histidine building block |
| Histidine-Containing Peptides | Introduces protected imidazole functionality |
| Metal-Binding Peptides | Supports design of peptides containing coordination motifs |
| Enzyme-Mimetic Peptides | Histidine can contribute acid/base catalytic functionality |
| Peptide Libraries | Enables sequence-diverse His-containing peptide synthesis |
| SAR Studies | Supports controlled variation of His residues |
| Custom Peptide Synthesis | Used in linear, cyclic and modified peptides |
Fmoc-His(Trt)-OH in Fmoc-SPPS
During synthesis, Fmoc-His(Trt)-OH is activated through the α-carboxyl group and incorporated into the growing peptide chain.
The Trt group remains on the imidazole during routine coupling and Fmoc-deprotection cycles and is removed during final acidic cleavage.
For routine room-temperature synthesis, Fmoc-His(Trt)-OH remains one of the most widely used histidine derivatives.
Histidine Racemization Is the Key Technical Consideration
Histidine deserves more attention than many routine Fmoc amino acids because it is particularly susceptible to racemization during activation and coupling.
A major Fmoc-SPPS review notes that conventional Fmoc-His(Trt)-OH can undergo significant racemization, particularly under slow or strongly base-mediated coupling conditions.
A 2022 process-development study specifically examined Fmoc-His(Trt)-OH and found that pre-activation conditions were critical: excessive pre-activation promoted histidine racemization, and the resulting D-His-containing impurity could be difficult to remove chromatographically.
This has an important practical consequence:
A high-purity Fmoc-His(Trt)-OH starting material does not by itself guarantee stereochemical integrity in the final peptide.
The coupling protocol also matters.
Practical Strategies for His-Containing Peptides
Factors that can increase epimerization risk include:
prolonged amino-acid pre-activation
strongly basic activation conditions
elevated coupling temperature
slow or sterically hindered coupling
poorly solvated or aggregated resin-bound peptide chains
Microwave-SPPS studies have likewise shown that histidine racemization can increase at high temperature, while lowering coupling temperature can reduce this problem.
Alan Scientific practical view: for high-value peptides containing histidine, stereochemical control should be considered part of the coupling protocol, not merely a raw-material specification.
Why Histidine Impurities Can Be Difficult to Detect
A D-His epimer has the same molecular formula and molecular mass as the corresponding L-His peptide.
Therefore, intact molecular-weight confirmation alone cannot establish histidine stereochemical purity.
In challenging applications, chromatographic separation or other stereochemically sensitive analytical methods may be necessary.
This is particularly relevant when high peptide purity is required, because an epimerized peptide impurity may have similar mass and similar chromatographic behavior to the desired sequence.
The Alan page currently lists “Optical Purity <0.3%.” I still recommend internally confirming that this means D-enantiomer / optical impurity <0.3% before standardizing the wording across product pages.
Product Documents
A Safety Data Sheet (SDS / MSDS) is available for this product to support laboratory handling, storage and safety assessment.
📎 MSDS_Fmoc-His(Trt)-OH_AS2034.pdf
Related Technical Resources
Explore Standard Fmoc-Amino Acids.
Read Amino Acids & Peptide Building Blocks.
Learn about Solid-Phase Peptide Synthesis (SPPS): A Practical Guide.
For challenging His-containing peptides, see Custom Peptide Synthesis.
Why Source Peptide Building Blocks from Alan Scientific?
Alan Scientific supplies protected amino acids and peptide building blocks for research applications, together with technical support for synthesis, purification and analytical QC.
Research Use Only