Ac-His-NHMe is an N-acetylated histidine derivative featuring the imidazole side chain characteristic of the histidine amino acid class, with the α-amino group capped as an acetamide and the α-carboxyl group converted to a primary amide via an NHMe (N-methylamide) functionality. The molecule therefore presents an imidazole ring for side-chain hydrogen bonding and acid-base behavior while lacking free amino and carboxyl groups, and its capped termini reduce undesired intermolecular reactivity relative to unprotected histidine. Ac-His-NHMe is used as a defined amino acid-amide building block or peptide-related intermediate in peptide chemistry and structure-reactivity studies where controlled terminal functionality and a histidine side chain are required for analytical method development, chemical biology labeling strategies, or the synthesis of more complex histidine-containing derivatives.
Ac-His-NHMe is an N-acetylated histidine amide featuring a methylamide at the C-terminus, which removes ionizable termini and presents histidine's imidazole side chain as the primary functional group for downstream chemistry. This capped, short peptidic motif is commonly used as a defined histidine-containing building block in chemical biology and peptide chemistry workflows where controlled side-chain reactivity and minimized backbone acid/base effects are advantageous. By providing a single, well-defined histidine environment without free N- or C-termini, Ac-His-NHMe supports reproducible assay conditions, method development, and intermediate preparation for histidine-modified peptides.
1. Histidine Side-Chain Modeling
Ac-His-NHMe is frequently used to model histidine behavior in systems where the imidazole side chain participates in coordination, protonation-dependent interactions, or site-specific derivatization. Researchers in chemical biology and protein chemistry use this capped histidine unit to probe how histidine's electronic and steric environment influences binding or reactivity while avoiding confounding effects from free amino and carboxyl groups. Because the backbone is protected as an acetamide and methylamide, the compound is also convenient for comparative studies of histidine analogs and for screening derivatization conditions that target the imidazole functionality.
2. Peptide Fragment Building Block
Ac-His-NHMe serves as a practical histidine-containing fragment for assembling short peptides and peptide-like structures in solution-phase workflows and in fragment coupling strategies. Peptide chemists and medicinal chemistry teams use this defined motif to introduce a histidine residue with controlled terminal chemistry, supporting the preparation of histidine-bearing intermediates and reference compounds used in SAR studies. The N-acetyl and C-methylamide capping pattern helps maintain a consistent local environment around the histidine side chain, which is valuable when downstream steps require reliable handling and reproducible analytical characterization of the intermediate.
3. Reaction Development Substrate
Ac-His-NHMe is utilized as a small, well-defined substrate for developing and optimizing chemistries that involve histidine-specific transformations, including imidazole-directed labeling and derivatization strategies. In analytical chemistry and chemical biology method development, the capped format reduces variability associated with terminal ionization, improving reproducibility when monitoring reaction progress by LC-MS or other chromatographic methods. Teams preparing standards for histidine-containing products also rely on this compound as a convenient reference material to validate derivatization efficiency and to confirm mass/fragmentation patterns for histidine-derived species.
4. Analytical Reference Compound
Ac-His-NHMe is commonly used as an analytical reference for characterizing histidine-containing peptide fragments, imidazole-modified products, and related reaction mixtures. Because it is a discrete, terminally capped histidine unit, it provides a consistent mass and fragmentation behavior that supports method calibration, identification of histidine-derived peaks, and verification of derivatization outcomes. Researchers performing LC-MS-based workflows in peptide chemistry, chemical biology, and pharmaceutical intermediate development use Ac-His-NHMe to benchmark retention behavior and to support the assignment of histidine-related signals in complex mixtures.
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