Product Name: Fmoc-Gly-Gly-OSu
Sequence: {Fmoc}-Gly-Gly-{OSu}
Purity: 98%
Form: White to off-white Solid
Storage : Sealed storage, away from moisture
CAS.NO.: 114726-49-7
CHEMICAl FORMULA: C23H21N3O7
Molar Mass: 451.43
SMILES: C1CC(=O)N(C1=O)OC(=O)CNC(=O)CNC(=O)OCC2C3=CC=CC=C3C4=CC=CC=C24
IUPACNAME: (2,5-dioxopyrrolidin-1-yl) 2-[[2-(9H-fluoren-9-ylmethoxycarbonylamino)acetyl]amino]acetate
INCHIKEY: YWPGJWLLWYHMEN-UHFFFAOYSA-N
INCHI: InChI=1S/C23H21N3O7/c27-19(24-12-22(30)33-26-20(28)9-10-21(26)29)11-25-23(31)32-13-18-16-7-3-1-5-14(16)15-6-2-4-8-17(15)18/h1-8,18H,9-13H2,(H,24,27)(H,25,31)
Application: Fmoc-Gly-Gly-OSu is an activated dipeptide building block used for the synthesis of ADC linkers and peptide-based conjugates. It contains an Fmoc-protected N-terminus and an OSu activated ester group, enabling efficient coupling reactions during linker construction. The Gly-Gly sequence provides a short, flexible spacer that can improve molecular spacing and support controlled conjugation design. Fmoc-Gly-Gly-OSu is widely used in peptide synthesis, medicinal chemistry, bioconjugation research, and antibody-drug conjugate development. It is valuable for preparing ADC linker intermediates, optimizing payload attachment strategies, and constructing functional peptide linkers for targeted drug delivery systems.
Current Research: Overview Fmoc-Gly-Gly-OSu is a protected activated dipeptide reagent that can be used to synthesize antibody-drug conjugate (ADC) linkers and related peptide-linker structures. The compound contains a Gly-Gly dipeptide unit, an Fmoc protecting group, and an N-hydroxysuccinimide ester, often abbreviated as OSu. This combination makes Fmoc-Gly-Gly-OSu useful in peptide chemistry, linker construction, and bioconjugation research. In ADC development, linker design is one of the most important factors controlling conjugate stability, payload release, pharmacokinetics, and therapeutic index. An ADC usually consists of an antibody, a linker, and a cytotoxic payload. The antibody provides targeting, the payload provides cell-killing activity, and the linker controls how the payload is attached and released. Fmoc-Gly-Gly-OSu is not a complete ADC linker by itself, but it can serve as a useful synthetic building block for preparing peptide-containing linker intermediates. The Gly-Gly motif is frequently used in linker chemistry because glycine is small, flexible, and minimally sterically demanding. Incorporating a Gly-Gly segment can help introduce conformational flexibility between functional groups, improve synthetic accessibility, and provide a short peptide spacer in drug-linker systems. Because Fmoc-Gly-Gly-OSu contains an activated ester, it is particularly suitable for coupling reactions with amino-containing molecules, allowing researchers to introduce a protected Gly-Gly unit into more complex linker structures. Structural Features of Fmoc-Gly-Gly-OSu Fmoc-Gly-Gly-OSu has three major structural elements: the Fmoc group, the Gly-Gly dipeptide, and the OSu activated ester. The Fmoc group, or 9-fluorenylmethoxycarbonyl group, is a widely used protecting group in peptide synthesis. It protects the N-terminus of the glycine-glycine dipeptide and allows controlled stepwise synthesis. Fmoc protection is commonly removed under mild basic conditions, making it compatible with many peptide synthesis workflows. In linker research, Fmoc protection allows the molecule to be incorporated into synthetic sequences while preventing unwanted side reactions at the amino terminus. The Gly-Gly unit provides a short and flexible peptide spacer. Glycine has no side chain beyond hydrogen, giving it high conformational freedom and low steric bulk. A Gly-Gly spacer can help separate two functional parts of a molecule without adding a large or rigid structural element. In ADC linker synthesis, this may be useful when researchers need a compact peptide segment between a payload, a self-immolative spacer, a cleavable peptide motif, or a conjugation handle. The OSu group is an N-hydroxysuccinimide ester. NHS esters are activated carboxylic acid derivatives that react efficiently with primary amines to form stable amide bonds. This makes Fmoc-Gly-Gly-OSu a convenient reagent for introducing the Fmoc-protected Gly-Gly sequence into amine-containing intermediates. In linker construction, this type of activated ester chemistry can simplify coupling steps and improve synthetic efficiency. Role in ADC Linker Synthesis Fmoc-Gly-Gly-OSu can be used to synthesize ADC linkers by providing a protected Gly-Gly dipeptide segment that can be coupled to other molecular components. In ADC linker design, short peptide spacers are often incorporated to regulate distance, flexibility, and release behavior. While Fmoc-Gly-Gly-OSu is not itself the final antibody-linker-payload construct, it can participate in the preparation of more advanced linker intermediates. For example, a researcher may use Fmoc-Gly-Gly-OSu to attach a Gly-Gly unit to an amino-containing payload intermediate or to a spacer that will later be connected to a cytotoxic drug. After coupling, the Fmoc group can be removed to expose the N-terminal amine, allowing further extension of the peptide linker or attachment to another functional group. This stepwise approach is common in linker synthesis, where multiple modules are assembled in a controlled sequence. The value of Fmoc-Gly-Gly-OSu lies in its dual function: it provides both a peptide spacer and an activated coupling site. This makes it useful for constructing linker systems that require precise peptide sequence installation. Importance of Peptide Linkers in ADC Research Peptide linkers are widely used in ADC research because they can be designed to respond to intracellular biological conditions. Many ADCs are internalized after binding to tumor-associated antigens and then trafficked to lysosomes. In lysosomal compartments, proteases can cleave certain peptide sequences, triggering release of the cytotoxic payload. Common cleavable peptide linkers include motifs such as Val-Cit, Val-Ala, and Gly-Phe-Leu-Gly or related sequences. Glycine-containing motifs are common because glycine can improve flexibility and spacing. While Fmoc-Gly-Gly-OSu provides only a Gly-Gly dipeptide unit, this unit can be incorporated into larger cleavable or non-cleavable linker structures. The design of peptide linkers must balance several requirements. The linker should remain stable during circulation to minimize premature payload release. It should be efficiently processed after internalization into target cells. It should not cause excessive hydrophobicity, aggregation, or poor conjugate behavior. It should also be compatible with the selected antibody, payload, and conjugation strategy. Fmoc-Gly-Gly-OSu contributes to this design space as a flexible peptide-building reagent. Synthetic Utility of the OSu Activated Ester One of the most important features of Fmoc-Gly-Gly-OSu is its activated ester functionality. The OSu group allows the carboxyl terminus of the Gly-Gly dipeptide to react with primary amines. This provides a direct route to amide bond formation, which is one of the most common linkages in peptide and drug-linker synthesis. Activated ester chemistry is useful because it can reduce the need for in situ coupling reagent activation. Instead of generating an activated carboxyl group during the reaction, the pre-activated OSu ester is already prepared for amine coupling. This can improve convenience and reproducibility in synthetic workflows. In ADC linker research, amide bonds are frequently used because they are generally stable under physiological conditions. By using Fmoc-Gly-Gly-OSu, researchers can introduce a stable Gly-Gly amide-linked spacer into linker intermediates. The resulting compound can then be further modified after Fmoc deprotection. Gly-Gly as a Flexible Spacer The Gly-Gly motif is valuable because it provides flexibility with minimal molecular bulk. In linker design, spacing is often critical. If a linker is too short or too rigid, it may prevent proper interaction between a payload and a release mechanism, or it may interfere with antibody conjugation. If a linker is too long or too hydrophobic, it may affect solubility, aggregation, or pharmacokinetics. A Gly-Gly spacer can help reduce steric hindrance while maintaining a compact linker structure. This is especially useful in drug-linker synthesis, where every added atom can influence molecular weight, hydrophobicity, and biological behavior. The small size of glycine makes Gly-Gly an attractive spacer for fine-tuning linker architecture. In peptide-drug conjugates and ADC linkers, Gly-Gly units may also be used as part of longer peptide sequences. For instance, glycine-rich segments can improve conformational freedom and provide access for enzymes or chemical release mechanisms. Fmoc-Gly-Gly-OSu is therefore useful for researchers who need to install this short spacer into a larger molecular design. Applications in Current Research Fmoc-Gly-Gly-OSu may be used in several areas of peptide and linker research. In ADC linker synthesis, it can serve as a building block for constructing peptide-containing linkers that connect antibodies to cytotoxic payloads. In drug-linker intermediate preparation, the OSu ester can react with amine-containing payloads, spacers, or self-immolative groups to form stable amide-linked products. In peptide-drug conjugate research, Fmoc-Gly-Gly-OSu may be used to introduce a flexible dipeptide spacer between a drug molecule and a targeting ligand. In solid-phase and solution-phase peptide chemistry, it can support stepwise assembly of protected peptide intermediates. In structure-activity relationship studies, researchers may compare Gly-Gly-containing linkers with other short spacers to evaluate the influence of linker flexibility, length, and composition on conjugate behavior. Research Considerations Researchers using Fmoc-Gly-Gly-OSu should consider its chemical reactivity and handling requirements. Activated esters can be sensitive to moisture and hydrolysis, so dry conditions and appropriate storage are usually important. Hydrolysis of the OSu ester can reduce coupling efficiency and lead to unwanted byproducts. The choice of solvent, base, reaction temperature, and amine partner can affect coupling yield. Because NHS ester reactions are typically directed toward primary amines, researchers should evaluate whether other nucleophilic groups are present in the reaction mixture. Selectivity may depend on the substrate and reaction conditions. Fmoc deprotection should also be carefully controlled. After coupling, the Fmoc group can be removed to expose the free amine for additional linker extension. However, downstream components must be compatible with the deprotection conditions. For ADC-related applications, analytical characterization is essential. Researchers may use HPLC, LC-MS, NMR, peptide mapping, and purity analysis to confirm identity, coupling efficiency, and product quality. When incorporated into antibody-drug conjugates, additional assays such as hydrophobic interaction chromatography, size-exclusion chromatography, drug-to-antibody ratio analysis, plasma stability testing, and cell-based cytotoxicity assays may be required. Future Research Directions As ADC technology continues to advance, linker design is becoming increasingly precise. Researchers are no longer treating linkers as passive connectors. Instead, linkers are engineered to control stability, release rate, solubility, aggregation, bystander activity, and tissue distribution. Small peptide-building reagents such as Fmoc-Gly-Gly-OSu support this work by enabling modular linker synthesis. Future research may continue to explore how short glycine-rich spacers affect ADC linker performance. Gly-Gly units may be compared with other spacer motifs, including Gly-Ser, β-alanine, aminohexanoic acid, polyethylene glycol-based spacers, and more rigid aromatic groups. These comparisons can help researchers identify optimal linker designs for specific payloads and antibody targets. Fmoc-Gly-Gly-OSu may also be useful in the development of peptide-drug conjugates beyond ADCs, including targeted small-molecule conjugates, ligand-drug conjugates, imaging probes, and protease-responsive delivery systems. Its simple structure, flexible spacer motif, and activated ester chemistry make it a practical reagent for expanding linker diversity. Conclusion Fmoc-Gly-Gly-OSu is a protected activated dipeptide reagent that can be used to synthesize ADC linkers and related peptide-linker intermediates. Its structure combines an Fmoc-protected N-terminus, a flexible Gly-Gly spacer, and an OSu activated ester suitable for amide bond formation. In current ADC and peptide-drug conjugate research, Fmoc-Gly-Gly-OSu is valuable as a modular building block for constructing linker systems with controlled spacing and synthetic flexibility. It can help introduce a compact dipeptide spacer into drug-linker intermediates, support further peptide extension after Fmoc deprotection, and contribute to the development of more refined linker-payload architectures. As antibody-drug conjugates and targeted delivery technologies continue to evolve, reagents such as Fmoc-Gly-Gly-OSu will remain useful tools for linker optimization, peptide spacer design, and next-generation bioconjugation research.
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