Fmoc-Gly-Gly-OH

Fmoc-Gly-Gly-OH is a versatile dipeptide linker component widely used in the construction of proteolytically cleavable ADC linker systems for targeted cancer therapy research. In ADC development, Fmoc-Gly-Gly-OH serves as the protected precursor to the Gly‑Gly dipeptide linker — a sequence that is selectively recognized and cleaved by lysosomal proteases such as cathepsin B, enabling the controlled intracellular release of cytotoxic payloads within target cancer cells after ADC internalization . The Fmoc group of Fmoc-Gly-Gly-OH protects the N‑terminal amine during synthesis and can be removed under mild basic conditions (20% piperidine in DMF) when the linker is ready for conjugation to an antibody. The small, flexible structure of Fmoc-Gly-Gly-OH enables efficient enzymatic cleavage kinetics and high drug loading efficiency, making Fmoc-Gly-Gly-OH an ideal building block for both in vitro and in vivo ADC applications. In addition to ADC applications, Fmoc-Gly-Gly-OH is also used as a protected dipeptide building block in SPPS, where its incorporation reduces the number of coupling steps required and improves synthesis efficiency for sequences containing Gly‑Gly motifs. Fmoc-Gly-Gly-OH is available at ≥98% HPLC purity from Cosperpharm, with full analytical characterization and batch traceability to support both research‑scale discovery and GMP‑grade manufacturing.

Product Parameters

Product Advantages

1. Proteolytically Cleavable ADC Linker. Fmoc-Gly-Gly-OH is a key component for constructing cleavable linkers in antibody‑drug conjugates. The Gly‑Gly dipeptide sequence is selectively recognized and cleaved by lysosomal proteases such as cathepsin B, enabling the controlled intracellular release of cytotoxic payloads within target cancer cells after ADC internalization. This targeted drug release mechanism minimizes off‑target toxicity and enhances therapeutic efficacy — making Fmoc-Gly-Gly-OH an essential building block for next‑generation ADC development.

2. Dual Functionality: ADC Linker and SPPS Building Block. Fmoc-Gly-Gly-OH is distinguished by its dual functionality. In ADC development, the Fmoc group protects the N‑terminal amine during linker synthesis and can be removed under mild basic conditions when ready for antibody conjugation. In peptide synthesis, Fmoc-Gly-Gly-OH can be incorporated directly into growing peptide chains as a dipeptide unit — reducing the number of coupling steps and improving synthesis efficiency for sequences containing Gly‑Gly motifs.

3. Small, Flexible Structure Enables Efficient Cleavage. The small, flexible dipeptide backbone of Fmoc-Gly-Gly-OH enables rapid access of lysosomal proteases to the cleavage site, ensuring efficient drug release kinetics. The glycine‑glycine sequence lacks bulky side chains that could sterically hinder enzymatic recognition, making Fmoc-Gly-Gly-OH one of the most reliable and widely used cleavable linker motifs in ADC design.

4. High Purity with Very Low Impurity Levels. Cosperpharm supplies Fmoc-Gly-Gly-OH at ≥98% HPLC purity as standard, with higher purity grades (≥99% or even ≥99.98%) available upon request. The compound is manufactured to very low levels of dipeptide byproducts, free‑amino acids, and acetic acid impurities — ensuring clean reaction profiles and minimal purification burden downstream.

5. Broad Utility in Targeted Cancer Therapy. Fmoc-Gly-Gly-OH is widely used in the development of antibody‑drug conjugates for targeted cancer therapy research. Its application facilitates the controlled release of cytotoxic payloads in both in vitro and in vivo experimental models, making it a versatile tool for ADC discovery and optimization across a range of cancer targets.

6. Excellent Solubility in Organic Solvents. Fmoc-Gly-Gly-OH demonstrates excellent solubility in DMF (0.3 g in 2 mL DMF), DMSO (10 mM), and methanol — the common solvent systems used in both peptide synthesis and ADC linker construction. This solubility profile enables high‑loading conjugation reactions and efficient synthesis workflows without precipitation issues.

Synthetic Routine

The general procedure for synthesizing N-fluoromethoxycarbonyl-glycylglycine using diglycin and 9-fluoromethylchloroformate as starting materials is as follows: Add 15 mL of dioxane to a mixture of diglycin (1 mmol) and 9-fluoromethylchloroformate (1.2 mmol), cool to 0 °C, then slowly add an equal volume of 1 M Na₂CO₃ solution. Stir the reaction mixture at room temperature for 12 hours. Monitor the reaction progress by thin-layer chromatography (TLC); upon completion, acidify the solution with 1 M HCl to pH 4–5. Extract the reaction mixture with ethyl acetate (3 × 70 mL) at 0 °C. Combine the organic phases, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to yield pure N-fluoromethoxycarbonyl-glycylglycine with a yield of 89%.

Storage Conditions

Store Fmoc-Gly-Gly-OH in a tightly sealed container under inert atmosphere (nitrogen or argon) at −20 °C for long‑term storage or at 2–8 °C (refrigerated) for short‑term storage (up to 6 months). For laboratory use, storage at 0–10 °C or 2–8 °C is acceptable. Keep the container dry, protected from light, and stored in a clean, well‑ventilated area away from strong oxidizing agents and sources of moisture. Fmoc-Gly-Gly-OH is moisture‑sensitive and heat‑sensitive — desiccated storage under inert gas is strongly recommended. Allow the sealed container to reach ambient temperature before opening to minimize moisture condensation [10†L8-L9][11†L7-L10][12†L13-L14].

Shelf life: 2–3 years when stored at −20 °C in a sealed container under inert atmosphere; 6–12 months when stored at 2–8 °C.

Handling precautions: Use only in a fume hood. Wear chemical‑resistant gloves (tested against EN 374 or equivalent), safety goggles, and a lab coat. Avoid generating dust or aerosols. Do not eat, drink, or smoke in work areas. After handling, wash hands thoroughly. Contaminated clothing should be removed and washed before reuse. Refer to the Safety Data Sheet (SDS) for complete safety information.

Special note for ADC applications: When opening containers of Fmoc-Gly-Gly-OH for ADC linker synthesis, work in a low‑humidity environment (glove box or dry box) to prevent moisture absorption, which can affect coupling efficiency and product quality.

Contact Us

Need a trusted source of Fmoc-Gly-Gly-OH for your ADC linker development or peptide synthesis project? Cosperpharm delivers high‑purity dipeptide building blocks with the analytical documentation, supply flexibility, and technical expertise that pharmaceutical manufacturers and research organizations rely on. From research quantities for proof‑of‑concept studies to bulk shipments for commercial ADC manufacturing, our team is ready to provide detailed pricing, lead times, and documentation support. Reach out to us today to discuss your requirements.