Fmoc-D-citrulline is a protected amino acid derivative in which citrulline bears an N-(9H-fluoren-9-ylmethoxycarbonyl) (Fmoc) protecting group on the alpha-amino function and is present as the D-stereoisomer. The molecule contains a free carboxylic acid and a side chain with a urea-like functionality (carbamoyl-substituted amino group) that can participate in hydrogen bonding and polar interactions, while the Fmoc group masks the amino group to control chemoselectivity during peptide assembly. In synthesis and chemical biology workflows, Fmoc-D-citrulline is used as a building block for stepwise peptide synthesis and for preparing citrulline-containing peptide or amino-acid conjugates used in structure-activity studies, labeling strategies, and analytical method development.
CAT No: CP04703
CAS No:200344-33-8
Synonyms/Alias:Fmoc-D-Cit-OH;200344-33-8;Fmoc-D-citrulline;(R)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-5-ureidopentanoicacid;C21H23N3O5;(R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-ureidopentanoicacid;Fmoc-D-Cit;AmbotzFAA1313;PubChem17238;MolPort-008-267-638;ZINC2517151;CF-645;AM82462;AJ-37038;AK-49541;KB-52036;SC-10124;FT-0643867;B-7716;I06-1181;J-300337
Fmoc-D-citrulline is an Fmoc-protected D-configured amino acid derivative in which the ureido-bearing side chain of citrulline is preserved while the α-amino group is masked as an N-(9H-fluoren-9-ylmethoxycarbonyl) carbamate. The molecule contains a stereogenic center at the α-carbon, a carboxylic acid functionality, and a highly polar urea/ureido motif that can participate in hydrogen-bonding and subsequent chemical transformations. The Fmoc group is base-labile under standard peptide-synthesis conditions, enabling controlled N-deprotection without disrupting the side-chain ureido functionality. The combination of a protected amino acid backbone and a reactive, side-chain urea functionality makes Fmoc-D-citrulline suitable for peptide building block preparation, chiral intermediate design, and downstream derivatization strategies that retain stereochemical integrity.
1. Peptide Synthesis
Fmoc-D-citrulline is used in peptide synthesis workflows where an Fmoc-protected amino acid building block is required for stepwise N-terminal assembly. The Fmoc carbamate enables orthogonal deprotection to expose the D-α-amino group for peptide coupling, while the ureido side chain provides a strongly hydrogen-bonding residue that can influence folding and binding in peptide analogs. The carboxylic acid and protected amine arrangement supports conventional amide bond formation strategies used for constructing peptide sequences containing citrulline residues. Incorporation of the D-stereocenter can be applied to generate stereochemically defined peptides for mechanistic studies, peptide stability assessment, and structure-guided scaffold optimization in peptide science.
2. Chemical Biology
Fmoc-D-citrulline functions as a chemical biology reagent for studying arginine/ureido recognition motifs and for probing how ureido-containing side chains affect molecular recognition. The ureido functionality can be leveraged for conjugation-compatible derivatization routes, while the Fmoc-protected backbone supports controlled introduction into peptides, peptidomimetics, or protein-facing probes. D-citrulline stereochemistry can be employed to tune binding selectivity and to reduce susceptibility to proteolysis when designing labeling reagents or molecular probes. Downstream products can include citrulline-containing peptide mimics and chemically defined biomolecule constructs used in receptor mapping, interaction assays, and mechanistic investigations of hydrogen-bond-driven recognition.
3. Side-Chain Functionalization
Fmoc-D-citrulline is applied in side-chain functionalization chemistry where the ureido motif serves as a handle for targeted derivatization beyond simple peptide incorporation. The side-chain urea/ureido group can participate in controlled transformations such as selective N-functionalization or conversion to analogs that modulate polarity, charge distribution, and hydrogen-bonding patterns. Fmoc protection of the α-amino group provides a stable platform during multistep synthesis, allowing selective manipulation of the ureido side chain while maintaining the chiral center. Resulting derivatives can be used as intermediates for peptidomimetic construction, SAR-focused analog libraries, and fine chemical synthesis of stereochemically defined citrulline-based building blocks.
4. Peptidomimetics And SAR
Fmoc-D-citrulline is utilized in peptidomimetic and SAR studies where stereodefined citrulline residues are incorporated to map structure-function relationships in bioactive peptide frameworks. The combination of an Fmoc-protected amino acid core and an unmasked ureido side chain supports the synthesis of constrained analogs that preserve key hydrogen-bonding features while altering stereochemistry through the D configuration. The ureido group can be retained as a polar interaction element or transformed into analogs that adjust donor/acceptor patterns for binding studies. Downstream use includes generating peptide analog series for SAR investigations, enabling systematic evaluation of how stereochemistry and side-chain functionality influence molecular recognition.
5. Pharmaceutical Manufacturing
Fmoc-D-citrulline is suitable for pharmaceutical manufacturing-oriented peptide intermediate preparation where controlled, reproducible building blocks are required for process-scale peptide synthesis. The Fmoc group provides a robust protection strategy for the α-amino functionality, supporting predictable deprotection and coupling cycles during manufacturing of citrulline-containing peptide intermediates. The ureido side chain contributes strong polarity that can affect solubility and purification behavior, making it relevant for defining manufacturing-ready synthetic routes and intermediate specifications. D-citrulline incorporation can also be used in industrial peptide design to produce stereochemically defined intermediates for analytical method development, reference standards, and downstream production of peptide-based ingredients or research-grade materials.
6. Analytical Standards
Fmoc-D-citrulline is employed in analytical research for preparing stereochemically defined reference materials and calibration supports related to citrulline-containing peptides and derivatives. The Fmoc-protected amino acid form enables consistent incorporation into model peptides, allowing formation of defined standards with the D-ureido residue positioned at specific sequence contexts. The ureido side chain's strong hydrogen-bonding character can improve detectability in targeted LC-MS or derivatization-based workflows used to monitor citrulline incorporation and stability. Downstream relevance includes supporting method development, impurity profiling, and structural verification of peptide intermediates and final peptide products that contain citrulline stereocenters.
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