Fmoc-His(Fmoc)-OPfp

Fmoc-His(Fmoc)-OPfp is a doubly Fmoc-protected histidine derivative bearing an OPfp (pentafluorophenyl ester) activated carboxylate, providing a protected amino acid building block for controlled peptide coupling and downstream functional transformations. The imidazole side chain of histidine is protected with an Fmoc group, preserving stereochemical integrity at the α-carbon while modulating nucleophilicity and minimizing side reactions during amide bond formation. The OPfp ester introduces an activated acyl leaving group well matched to peptide coupling workflows, while the two Fmoc groups enable orthogonal deprotection strategies to reveal the α-amino functionality and the side-chain imidazole for selective further chemistry. The presence of multiple aromatic protecting groups and the pentafluorophenyl ester motif gives a defined reactivity profile that supports stepwise synthesis of protected peptides, peptidomimetics, and functionalized histidine-containing intermediates.

1. Peptide Synthesis

Fmoc-His(Fmoc)-OPfp is used in peptide synthesis as a histidine-based, N- and side-chain-protected building block whose OPfp-activated carboxylate can participate in amide bond formation under coupling conditions compatible with Fmoc strategies. The α-amino group is masked as an Fmoc carbamate, while the imidazole side chain is also Fmoc-protected, reducing undesired imidazole acylation or coordination during chain assembly. The activated OPfp ester can be converted into the corresponding amide linkage efficiently in stepwise solid-phase or solution-phase peptide construction, enabling the incorporation of histidine residues with controlled protection patterns. Downstream, sequential Fmoc deprotection can expose the imidazole for subsequent side-chain modifications or for generating histidine-rich peptide architectures used in biochemical research and synthetic methodology development.

2. Side-Chain Functionalization

Fmoc-His(Fmoc)-OPfp supports side-chain functionalization workflows where histidine's imidazole must be preserved until a planned modification step. Dual Fmoc protection keeps the imidazole nitrogen atoms from reacting prematurely, while the OPfp ester functionality enables conversion into peptide or intermediate amides before selective deprotection. After orthogonal removal of the relevant Fmoc groups, the liberated imidazole can be targeted for controlled derivatization such as nucleophilic substitution, coordination chemistry, or further protection for multistep syntheses. The resulting functionalized histidine-containing derivatives can serve as precursors for peptidomimetics, enzyme-binding probes, or structure-encoded scaffolds in chemical biology and peptide science.

3. Bioconjugation Chemistry

Fmoc-His(Fmoc)-OPfp is applicable to bioconjugation chemistry where protected histidine residues are incorporated into peptide handles prior to conjugation to biomolecules. The OPfp ester provides an activated acyl intermediate that can be transformed into stable amide linkages, allowing attachment of histidine-containing motifs to targeting peptides, linkers, or carrier constructs while maintaining side-chain protection during conjugation setup. Fmoc groups enable stepwise unveiling of reactive amines or imidazole functionality, supporting controlled conjugation chemistries that minimize heterogeneity from uncontrolled side reactions. Downstream processing can yield defined histidine-bearing conjugates suitable for analytical studies, affinity reagents, and molecular recognition experiments that rely on imidazole participation or pH-responsive behavior.

4. Process Chemistry Intermediate

Fmoc-His(Fmoc)-OPfp is suitable for process chemistry intermediate preparation in fine chemical manufacturing due to its clear functional-group inventory: two Fmoc protecting groups and an OPfp activated ester that can be handled as a discrete acylating synthon. The OPfp leaving group and aromatic protecting groups can be leveraged to design manufacturing routes that separate activation and coupling steps, improving control over impurity profiles arising from premature hydrolysis or side-chain reactivity. Fmoc deprotection steps provide a predictable handle for sequential unmasking of the α-amino group and the histidine imidazole, supporting scalable synthesis of protected peptide building blocks and downstream coupling intermediates. The compound's defined stereochemical and protection pattern makes it a practical intermediate for producing histidine-containing peptide fragments used across peptide manufacturing and custom synthesis operations.

5. Analytical Research Standards

Fmoc-His(Fmoc)-OPfp can be employed in analytical research as a chemically defined histidine derivative standard for monitoring protection, activation, and deprotection states during amino acid and peptide workflows. The combination of Fmoc-protected α-amino functionality, Fmoc-protected imidazole side chain, and OPfp ester activation creates distinguishable chemical signatures that can be tracked by chromatographic and spectrometric methods to verify intermediate identity. The pentafluorophenyl ester motif can also facilitate method development for detecting activated acyl species and for calibrating analytical responses associated with peptide coupling precursors. Use in analytical method qualification and intermediate characterization supports reproducible peptide building block preparation and quality control in research-grade amino acid chemistry and peptide process development.

1. Exosomes-mediated Transfer of miR-125a/b in Cell-to-cell Communication: A Novel Mechanism of Genetic Exchange in the Intestinal Microenvironment

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

3. High fat diet and GLP-1 drugs induce pancreatic injury in mice

4. Effect of Probiotic Lactobacillus plantarum on Streptococcus mutans and Candida albicans Clinical Isolates from Children with Early Childhood Caries

5. The effect of sex on immune responses to a homocitrullinated peptide in the DR4-transgenic mouse model of Rheumatoid Arthritis