L-2-Thiolhistidine contains the histidine amino acid backbone with a side chain bearing a thiol group at the 2-position relative to the imidazole ring, classifying it as a thiol-substituted, proteinogenic-like amino acid analogue. The molecule possesses both an amino functional group and a carboxyl functional group, and the imidazole and thiol functionalities provide complementary acid-base and nucleophilic character while the "L-" designation specifies the stereochemical form of the amino acid center. L-2-Thiolhistidine is used as a building block for peptide and peptidomimetic synthesis where a reactive thiol handle is required, and it also supports chemical labeling, conjugation, and structure-activity studies that depend on thiol-containing side chains.
CAT No: CP24402
L-2-Thiolhistidine is an L-configured histidine derivative bearing a side-chain thiol at the 2-position of the imidazole-containing amino acid framework, providing both an imidazole nitrogen set and a reactive sulfur nucleophile within a single chiral amino acid. The molecule contains the amino and carboxylic acid functionality typical of amino acid building blocks, enabling conversion to protected forms for peptide coupling or to salts/esters for controlled reactivity. The thiol group can participate in thioether formation, disulfide exchange, and selective oxidation-reduction chemistry, while the imidazole moiety can engage in acid-base equilibria and metal coordination relevant to biomolecular recognition. As a chiral sulfur-containing amino acid intermediate, L-2-Thiolhistidine can serve as a chemically defined handle for downstream derivatization, peptide analog construction, and biochemical probe development where thiol-specific reactivity is required.
1. Peptide Synthesis
L-2-Thiolhistidine supports peptide building workflows where histidine-like side-chain recognition and thiol chemistry must be preserved through coupling and subsequent transformations. The amino acid backbone enables standard amide bond formation, while the thiol side chain can be managed via protection strategies such as thioether or disulfide-type masking to prevent oxidation during activation and coupling. The imidazole ring can be retained or selectively protected to control reactivity during stepwise synthesis, allowing controlled incorporation of sulfur-containing residues into peptides and peptidomimetics. Downstream deprotection can regenerate the free thiol for disulfide formation, thioether conjugation, or redox-responsive functionality in the final peptide scaffold, aligning the residue with thiol-dependent biomolecular motifs.
2. Bioconjugation Chemistry
L-2-Thiolhistidine is applicable to chemical biology workflows that require site-selective thiol handles for conjugation and labeling. The side-chain thiol provides a nucleophilic sulfur center for forming thioether linkages, enabling coupling to electrophiles used in biomolecule labeling, surface functionalization, or affinity reagent construction. The imidazole-containing histidine framework can influence local microenvironment and binding behavior during conjugate assembly, supporting design of linkers that balance stability and reactivity. The amino acid nature also facilitates conversion into protected derivatives that can be incorporated into larger constructs, after which controlled deprotection can generate free thiol for conjugation steps, supporting downstream generation of defined bioconjugates and analytical standards.
3. Protein Engineering
L-2-Thiolhistidine can be used in protein engineering and enzyme studies where thiol-specific chemistry is required to probe structure-function relationships or to introduce redox-active sites. The L-stereochemistry provides a defined chiral residue that can be incorporated into peptide segments via amino acid derivative synthesis routes, enabling preparation of protein fragments, engineered domains, or thiol-functional peptide mimics. The imidazole and thiol combination can enable coordination-like interactions and redox behavior that mimic aspects of native sulfur-containing motifs, supporting mechanistic studies of catalytic residues or binding interfaces. The ability to generate and then manipulate a free thiol after assembly enables construction of protein-reactive probes, disulfide-linked variants, or thiol-dependent crosslinking reagents used to interrogate biomolecular conformations.
4. Peptidomimetics And SAR
L-2-Thiolhistidine is suitable for peptidomimetic construction and structure-activity relationship studies where thiol-bearing side chains are used to tune binding, stability, and chemical reactivity profiles. The amino acid backbone supports incorporation into constrained analogs through amide coupling strategies, while the thiol group can be used as a functional substituent for thioether formation, reversible disulfide linkage, or controlled oxidation-state modulation. The imidazole ring contributes an additional heteroaromatic recognition element that may affect hydrogen bonding and metal interactions in designed scaffolds. Downstream derivatization of the sulfur functionality allows generation of focused analog sets for SAR work, including thiol-reactive intermediates and oxidized/reduced variants that help map how sulfur chemistry impacts molecular recognition.
5. Process Chemistry Intermediates
L-2-Thiolhistidine serves as a chiral sulfur-containing amino acid intermediate for fine chemical synthesis and process chemistry routes that require controlled thiol handling. The presence of both carboxylic acid and primary amine groups supports conversion into protected amino acid derivatives, enabling compatibility with industrial peptide coupling conditions and subsequent deprotection steps designed around thiol stability. The thiol group can be managed through appropriate protection and oxidation-state control strategies to limit side reactions such as disulfide scrambling and over-oxidation during manufacturing-scale handling. The resulting protected/unprotected interconversion capability supports downstream preparation of thiol-functional building blocks, specialty chemical intermediates, and sulfur-containing amino acid derivatives used across peptide manufacturing and applied chemical synthesis.
6. Analytical Research Standards
L-2-Thiolhistidine can be employed in analytical research for method development and reference material preparation involving thiol quantification, derivatization-based detection, and amino acid profiling. The defined L-configuration and dual functional groups allow it to act as a chemically specific standard for monitoring thiol stability, oxidation state changes, and derivatization efficiency in complex matrices. The imidazole moiety can provide additional spectroscopic or chromatographic behavior distinct from non-imidazole thiol standards, supporting discrimination in analytical workflows. Conversion to protected or derivatized forms can further support calibration strategies for peptide hydrolysates, bioconjugate characterization, and redox-state tracking in biochemical research intermediate analysis.
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