Arg-Phe-Asp-Ser

Product Name: Arg-Phe-Asp-Ser

Sequence: Arg-Phe-Asp-Ser

Purity: 95%

Form: Solid

Storage : -20°C, sealed storage, away from moisture

CAS.NO.: 102567-19-1

CHEMICAl FORMULA: C22H33N7O8

Molar Mass: 523.54

SMILES: C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N

IUPACNAME: (3S)-3-[[(2S)-2-[[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]-4-[[(1S)-1-carboxy-2-hydroxyethyl]amino]-4-oxobutanoic acid

INCHIKEY: SAGYNNXCQOFQHW-VGWMRTNUSA-N

INCHI: InChI=1S/C22H33N7O8/c23-13(7-4-8-26-22(24)25)18(33)27-14(9-12-5-2-1-3-6-12)19(34)28-15(10-17(31)32)20(35)29-16(11-30)21(36)37/h1-3,5-6,13-16,30H,4,7-11,23H2,(H,27,33)(H,28,34)(H,29,35)(H,31,32)(H,36,37)(H4,24,25,26)/t13-,14-,15-,16-/m0/s1

Application: Arg-Phe-Asp-Ser is a cleavable ADC linker used in antibody-drug conjugate research and targeted drug delivery design. Its defined peptide sequence can be incorporated into drug-linker systems to support enzymatic cleavage and controlled payload release under specific biological conditions. As a peptide-based linker, Arg-Phe-Asp-Ser is valuable for studying linker stability, protease sensitivity, conjugate performance, and payload release mechanisms. It is widely used in medicinal chemistry, peptide synthesis, bioconjugation research, and ADC development, especially in studies focused on optimizing cleavable linker strategies for antibody-mediated delivery and cancer-related therapeutic platforms.

Current Research: Overview Arg-Phe-Asp-Ser, also written as RFDS, is a short peptide sequence that can be used as a cleavable ADC linker. It is composed of four amino acid residues: arginine, phenylalanine, aspartic acid, and serine. In antibody-drug conjugate research, cleavable peptide linkers are used to connect cytotoxic payloads to antibodies while enabling controlled drug release after the ADC reaches target cells. Antibody-drug conjugates, or ADCs, are designed to combine the targeting ability of monoclonal antibodies with the high potency of small-molecule payloads. The antibody recognizes a tumor-associated antigen, the payload provides cytotoxic activity, and the linker controls attachment and release. Although the linker is sometimes viewed as only a chemical bridge, it is one of the most important determinants of ADC stability, release behavior, therapeutic index, and biological performance. Arg-Phe-Asp-Ser is relevant to ADC design because peptide linkers can be engineered for enzymatic cleavage. After an ADC binds its target antigen and is internalized into tumor cells, intracellular proteases may process the peptide linker and trigger payload release. As a short cleavable peptide motif, Arg-Phe-Asp-Ser may be used in linker screening, drug-linker synthesis, payload release studies, and targeted cancer research. Structural Features of Arg-Phe-Asp-Ser The Arg-Phe-Asp-Ser sequence contains four chemically distinct residues, giving it a diverse physicochemical profile. Arginine is a basic amino acid with a positively charged guanidinium group. It can participate in electrostatic interactions and hydrogen bonding. In peptide linkers, arginine may influence solubility, enzyme recognition, and interaction with negatively charged biomolecules. Phenylalanine is an aromatic hydrophobic amino acid. It contributes hydrophobic character and may influence protease recognition, local peptide conformation, and interaction with protein binding pockets. Aromatic residues are often important in enzyme-substrate interactions because they can participate in hydrophobic and stacking interactions. Aspartic acid is an acidic amino acid with a negatively charged carboxylate side chain under many physiological conditions. Its presence gives the linker an anionic feature and may affect solubility, charge balance, and protease accessibility. Serine is a polar amino acid with a hydroxyl-containing side chain. It can participate in hydrogen bonding and may improve aqueous compatibility. Serine can also influence peptide conformation and enzymatic processing. Together, these residues form a compact tetrapeptide with basic, aromatic, acidic, and polar characteristics. This diversity may be useful in protease-responsive linker design, where both sequence recognition and molecular accessibility influence cleavage efficiency. Role as a Cleavable ADC Linker Arg-Phe-Asp-Ser is described as a cleavable ADC linker. Cleavable linkers are designed to remain stable during circulation but release the payload after the ADC enters target cells or reaches a specific biological environment. In peptide-based ADC linkers, release is often triggered by proteases found in lysosomes or tumor-associated compartments. The concept is straightforward but highly sensitive to molecular context. An ADC containing a cleavable peptide linker binds to a cell-surface antigen, undergoes internalization, and traffics to intracellular compartments. Proteases then cleave the linker sequence or a nearby peptide bond. If the linker is connected to a self-immolative spacer or properly designed payload attachment site, this cleavage event can lead to release of the active drug. Arg-Phe-Asp-Ser may therefore be used as part of a peptide linker system to study enzymatic cleavage and controlled payload release. However, its final behavior depends on the full linker-payload architecture, antibody conjugation site, drug-to-antibody ratio, payload structure, antigen internalization, and target-cell protease profile. For this reason, it is most accurate to describe Arg-Phe-Asp-Ser as a cleavable ADC linker motif or linker building block rather than as a complete ADC release system by itself. Importance of Cleavable Linkers in ADC Research Cleavable linkers are important because many ADC payloads are extremely potent and cannot be safely delivered as unconjugated systemic drugs. The linker must reduce premature payload exposure in normal tissues while allowing efficient drug release inside cancer cells. A poorly designed linker can compromise ADC performance. If the linker is too unstable, the payload may be released in plasma, increasing systemic toxicity. If the linker is too stable, the ADC may be internalized but fail to release enough active payload, reducing anticancer activity. The best linker design balances circulation stability with target-site activation. Peptide linkers are especially attractive because biological systems naturally contain enzymes that recognize peptide sequences. By selecting specific amino acid motifs, researchers can tune cleavage sensitivity, intracellular release rate, and conjugate stability. Arg-Phe-Asp-Ser contributes to this design space as a short peptide sequence that may be evaluated for protease-responsive release. Applications in ADC Linker-Payload Synthesis Arg-Phe-Asp-Ser may be used in the synthesis of ADC linker-payload intermediates. In a typical ADC development workflow, the peptide linker is chemically connected to a payload and an antibody-conjugation handle. The final linker-payload structure is then attached to an antibody through lysine residues, cysteine residues, engineered amino acids, or site-specific conjugation chemistry. Arg-Phe-Asp-Ser can provide the peptide-cleavable portion of such a linker. It may be combined with additional components such as: A conjugation handle, which enables attachment to an antibody or targeting molecule. A spacer, which improves distance, solubility, or enzyme accessibility. A self-immolative group, which helps release the free payload after peptide cleavage. A payload attachment group, which connects the cytotoxic agent to the linker. This modular structure allows researchers to tune the final ADC. The peptide sequence affects cleavage, while the spacer and conjugation chemistry influence solubility, stability, and pharmacokinetics. Relevance to Cancer Research ADCs are an important class of targeted cancer therapy platforms. They are designed to deliver cytotoxic agents preferentially to tumor cells expressing specific antigens. Cleavable ADC linkers such as Arg-Phe-Asp-Ser are relevant because they help control when and where the payload is released. In cancer research, peptide-cleavable linkers are commonly studied in cell-based assays, tumor models, plasma stability experiments, and protease cleavage assays. Researchers may evaluate whether the linker improves selective cytotoxicity against antigen-positive cells while reducing effects on antigen-negative cells. Arg-Phe-Asp-Ser may be studied in ADC systems containing different payload classes, including tubulin inhibitors, DNA-damaging agents, topoisomerase inhibitors, or other cytotoxic molecules. The ideal linker-payload design depends on the tumor target, internalization rate, payload potency, bystander effect requirements, and safety profile. Research Applications Arg-Phe-Asp-Ser may be useful in several ADC and bioconjugation research areas. In cleavable ADC linker synthesis, it can serve as the peptide sequence used to connect payload and antibody-linking components. In payload release studies, Arg-Phe-Asp-Ser-containing linkers may be tested for enzymatic cleavage and drug liberation. In protease-responsive drug delivery, the sequence may be evaluated as a trigger motif for controlled release. In linker optimization studies, it may be compared with other peptide linkers such as Val-Cit, Val-Ala, Gly-Gly-Phe-Gly, Gly-Phe-Leu-Gly, or Ala-Ala-Asn. In structure-activity relationship research, Arg-Phe-Asp-Ser may help researchers understand how charge, hydrophobicity, and polarity influence linker cleavage and ADC performance. In cancer drug delivery research, it may support the development of ADCs designed for selective intracellular activation. Research Considerations Researchers using Arg-Phe-Asp-Ser should evaluate several factors during ADC design. First, cleavage specificity should be experimentally validated. The sequence may be cleavable in a given system, but cleavage rate and selectivity depend on the protease environment and final linker structure. Second, plasma stability is essential. A useful ADC linker should resist premature cleavage in blood or storage conditions while remaining responsive after internalization. Third, payload attachment chemistry matters. Peptide cleavage must be connected to an efficient drug-release mechanism. In many ADC designs, a self-immolative spacer is needed to release the active payload after enzymatic cleavage. Fourth, charge balance should be considered. Arg-Phe-Asp-Ser contains both cationic and anionic residues, which may affect solubility, interaction with proteins, and chromatographic behavior. Fifth, steric accessibility is important. If the linker is buried near the antibody surface or blocked by a bulky payload, protease cleavage may be inefficient. Analytical and functional testing may include HPLC, LC-MS, peptide mapping, protease cleavage assays, plasma stability studies, hydrophobic interaction chromatography, size-exclusion chromatography, drug-to-antibody ratio analysis, binding assays, and cell-based cytotoxicity experiments. Future Research Directions ADC research is moving toward increasingly precise linker engineering. Instead of relying on a small number of standard linkers, researchers now evaluate peptide sequences based on target biology, payload type, tumor microenvironment, intracellular trafficking, and safety requirements. Arg-Phe-Asp-Ser may be valuable as part of this expanding linker toolkit. Future studies may compare Arg-Phe-Asp-Ser with established cleavable linkers to determine its relative stability, protease sensitivity, release kinetics, and influence on ADC activity. Researchers may also modify the sequence, add hydrophilic spacers, combine it with self-immolative groups, or adapt it to site-specific conjugation platforms. As more ADCs and targeted conjugates are developed, the demand for diverse cleavable peptide linkers will continue to grow. Short motifs such as Arg-Phe-Asp-Ser provide useful starting points for designing drug-linker systems with tuned release behavior. Conclusion Arg-Phe-Asp-Ser is a short peptide sequence that can be used as a cleavable ADC linker. Its four-residue structure combines basic, aromatic, acidic, and polar amino acids, giving it a chemically diverse profile for protease-responsive linker design. In current ADC research, Arg-Phe-Asp-Ser may be used in linker-payload synthesis, payload release studies, protease-cleavable drug delivery, and cancer-focused bioconjugation research. Its performance should be validated in the context of the complete ADC system, including antibody target, payload, conjugation chemistry, and intracellular processing. As antibody-drug conjugate technology continues to evolve, cleavable peptide linkers such as Arg-Phe-Asp-Ser remain important tools for improving controlled payload release and developing more selective targeted cancer therapeutics.