N-α-Acetyl-L-histidine monohydrate

N-α-Acetyl-L-histidine monohydrate is an N-acetylated L-histidine derivative in which the imidazole side chain remains free while the α-amino group is converted to an acetamide, yielding a stable, peptide-compatible amino acid form. The molecule bears a carboxylic acid functionality and a stereogenic center at the α-carbon in the L-configuration, with the imidazole ring providing pH-dependent basicity and metal-binding coordination potential. The monohydrate form introduces crystallization water that can influence handling and reproducibility in solid-state workflows, while the N-acetyl group modulates reactivity by suppressing direct amine coupling at the N-terminus. The combined presence of a protected/blocked α-amide nitrogen and an unprotected imidazole enables controlled derivatization, selective conjugation, and downstream transformation into histidine-containing peptide fragments and analytical standards.

1. Peptide Coupling

N-α-Acetyl-L-histidine monohydrate supports peptide synthesis workflows where an N-acetylated histidine residue is required as a defined N-terminal or internal building block. The acetamide at the α-position reduces undesired N-alkylation or side reactions during coupling, while the free carboxylic acid and stereochemistry at the α-carbon allow incorporation into histidine-containing sequences via standard protected amino acid chemistry. The imidazole side chain can participate in coordination-controlled conformations and can remain available for orthogonal protection or selective functionalization depending on the coupling strategy. The resulting histidine-containing intermediates can be used to construct peptide analogs, study terminal modifications, and generate defined fragments for structure-activity relationship studies.

2. Chemical Biology Labeling

N-α-Acetyl-L-histidine monohydrate is applicable to chemical biology and biomolecule labeling strategies that exploit histidine's imidazole for selective binding and reaction targeting. The intact imidazole ring can be used as a recognition handle for affinity-based workflows or for designing conjugates where imidazole participates in reversible interactions with metal ions or receptor-like motifs. The N-acetylation at the α-amino position provides a controlled amide environment that can reduce background reactivity relative to free amino histidine, improving compatibility with labeling sequences that require side-chain selectivity. The carboxylic acid enables further activation to form amide or ester linkages for attaching to probes, scaffolds, or carrier molecules used in biochemical research.

3. Analytical Reference Standards

N-α-Acetyl-L-histidine monohydrate functions as an analytical research reference for amino acid profiling, derivatization method development, and method validation in histidine chemistry. The defined L-stereochemistry and N-acetylation state create a distinct chromatographic and mass-spectrometric signature compared with unmodified histidine, supporting unambiguous identification in complex matrices. The monohydrate form can be leveraged to standardize solid-state behavior when preparing calibration materials or internal standards for LC-MS and related analytical platforms. The imidazole side chain's pH-dependent behavior can also be used to evaluate ionization trends and derivatization conditions that target histidine residues in peptide hydrolysates.

4. Side-Chain Functionalization

N-α-Acetyl-L-histidine monohydrate enables side-chain functionalization routes centered on the imidazole group while maintaining the α-amide as a stable, non-nucleophilic handle. The free imidazole can be selectively engaged for coordination chemistry, electrophile-driven derivatization, or conversion into imidazole-substituted intermediates used in peptidomimetic construction. The N-acetylated backbone helps maintain chemoselectivity by limiting competing reactions at the α-amino position, supporting cleaner downstream transformations. The carboxylic acid allows activation to generate coupling-ready derivatives for attaching functionalized histidine analogs to polymers, linkers, or scaffold molecules.

5. Pharmaceutical Intermediate Preparation

N-α-Acetyl-L-histidine monohydrate is suitable for process chemistry intermediate preparation where a defined N-acetylated amino acid motif is required for synthetic sequences toward peptide-like or histidine-containing structures. The N-acetyl group provides an amide-stabilized nitrogen that can be carried through multi-step syntheses without requiring repeated N-protection, while the L-configuration supports stereochemically consistent incorporation into later coupling stages. The imidazole ring can be managed through orthogonal protection or controlled reactivity to match the protection/deprotection logic of peptide synthesis and medicinal chemistry building blocks. The compound's functional group set supports conversion into activated carboxylic acid derivatives and subsequent formation of amide-linked intermediates used in fine chemical and pharmaceutical intermediate manufacturing.

6. Industrial Biocatalysis Substrate

N-α-Acetyl-L-histidine monohydrate can be employed in industrial biocatalysis and specialty chemical production contexts involving histidine-dependent transformations. The N-acetylated α-amide and free imidazole create a substrate profile that may influence enzyme recognition, particularly in processes that differentiate N-terminal acetylation states or require an imidazole-bearing amino acid substrate. The stereochemical integrity at the α-carbon can be maintained during enzymatic conversions, supporting downstream isolation of stereochemically consistent products. The resulting functionalized amino acid derivatives can serve as intermediates for generating histidine-containing small molecules, peptide analogs, or functional materials where imidazole-mediated coordination or binding is a design element.

1. Myotropic activity of allatostatins in tenebrionid beetles

2. Myotropic activity and immunolocalization of selected neuropeptides of the burying beetle Nicrophorus vespilloides (Coleoptera: Silphidae)

3. An Isolated TCR αβ Restricted by HLA-A* 02: 01/CT37 Peptide Redirecting CD8+ T Cells to Kill and Secrete IFN-γ in Response to Lung Adenocarcinoma Cell Lines

4. The spatiotemporal control of signalling and trafficking of the GLP-1R

5. Store-operated Ca2+ entry sustains the fertilization Ca2+ signal in pig eggs