Product Name: Gly-Gly-Phe-Gly
Sequence: GGFG
Purity: 99%
Form: White to off-white Solid
Storage : Sealed storage, away from moisture and light
CAS.NO.: 200427-88-9
CHEMICAl FORMULA: C15H20N4O5
SMILES: C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)O)NC(=O)CNC(=O)CN
IUPACNAME: 2-[[(2S)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-phenylpropanoyl]amino]acetic acid
INCHIKEY: HXUVTXPOZRFMOY-NSHDSACASA-N
INCHI: InChI=1S/C15H20N4O5/c16-7-12(20)17-8-13(21)19-11(15(24)18-9-14(22)23)6-10-4-2-1-3-5-10/h1-5,11H,6-9,16H2,(H,17,20)(H,18,24)(H,19,21)(H,22,23)/t11-/m0/s1
Molar Mass: 336.34
Application: Gly-Gly-Phe-Gly is a protease-cleavable peptide spacer widely used in antibody-drug conjugate (ADC) linker design. This short GGFG sequence can be incorporated between an antibody and a cytotoxic payload to support controlled enzymatic release of the drug in target cells or tumor-associated environments. Gly-Gly-Phe-Gly is also applicable to Doxorubicin (DXR) conjugates, where linker chemistry influences payload stability, release efficiency, and conjugate performance. As an ADC linker, Gly-Gly-Phe-Gly is valuable for medicinal chemistry, peptide synthesis, bioconjugation research, and ADC development, including synthesis strategies for conjugates such as Puxitatug samrotecan.
Current Research: Overview Gly-Gly-Phe-Gly, also known as GGFG, is a short tetrapeptide composed of glycine-glycine-phenylalanine-glycine. It is widely described as a peptide spacer and ADC linker intermediate. Product references list Gly-Gly-Phe-Gly as applicable to Doxorubicin (DXR) conjugates, and it can also be used as an ADC linker for the synthesis of antibody-drug conjugates, including Puxitatug samrotecan, also known as AZD8205. In current cancer drug delivery research, peptide spacers such as Gly-Gly-Phe-Gly are important because they help connect cytotoxic payloads, polymer carriers, antibodies, or other targeting structures. Instead of acting as a passive chemical bridge, a peptide spacer can influence drug release, molecular stability, pharmacokinetic behavior, and tumor-selective activation. Gly-Gly-Phe-Gly is especially relevant in research on macromolecular prodrugs, Doxorubicin conjugates, and antibody-drug conjugates (ADCs), where linker design is one of the key determinants of therapeutic performance. Structural Characteristics of Gly-Gly-Phe-Gly Gly-Gly-Phe-Gly contains four amino acid residues: two glycine residues at the N-terminal side, one phenylalanine residue, and one glycine residue at the C-terminal side. The molecular formula is commonly listed as C15H20N4O5, with a molecular weight of 336.34 g/mol and CAS number 200427-88-9. The sequence design gives the molecule several useful features. Glycine is the smallest amino acid and provides conformational flexibility. The two N-terminal glycine residues may help the spacer adopt flexible conformations between a carrier and a payload. Phenylalanine introduces an aromatic hydrophobic side chain, which can influence enzyme recognition, linker accessibility, and molecular interaction with neighboring chemical groups. The final glycine residue contributes additional flexibility and may serve as a terminal site for further chemical modification depending on the synthetic strategy. Because of this balance between flexibility and hydrophobic character, Gly-Gly-Phe-Gly is useful as a short spacer in drug conjugation systems. It is not simply a long inert linker; instead, its amino acid composition may help regulate how the drug conjugate is processed under biological or enzymatic conditions. Gly-Gly-Phe-Gly in Doxorubicin Conjugate Research One of the major research applications of Gly-Gly-Phe-Gly is in Doxorubicin conjugates. Doxorubicin is an anthracycline anticancer agent widely used in oncology research, but its clinical use is limited by systemic toxicity, especially cardiotoxicity. Drug conjugation strategies have therefore been developed to improve tumor targeting, alter biodistribution, and control drug release. Gly-Gly-Phe-Gly has been reported as a peptide spacer applicable to Doxorubicin conjugates. One referenced study investigated peptide spacers controlling drug release from a macromolecular prodrug system based on carboxymethyldextran polyalcohol-peptide-drug conjugates. In this type of system, the peptide spacer helps connect the polymer carrier to the cytotoxic drug. The spacer can influence when and where the active drug is released, which is a central question in prodrug design. For Doxorubicin conjugates, a peptide spacer must satisfy several design requirements. It should be chemically compatible with conjugation chemistry, stable enough to avoid premature drug release in circulation, and sufficiently cleavable or processable in target tissues or intracellular compartments. A spacer that releases Doxorubicin too early may increase systemic toxicity, while a spacer that is too stable may reduce antitumor activity. Gly-Gly-Phe-Gly is therefore useful as a research tool for studying the relationship between spacer structure and controlled drug release. Role as an ADC Linker Gly-Gly-Phe-Gly is also used as an ADC linker. Antibody-drug conjugates are targeted therapeutic constructs that combine an antibody, a linker, and a cytotoxic payload. The antibody directs the conjugate to tumor-associated antigens, while the linker controls payload attachment and release. Linker chemistry is critical because it influences circulation stability, intracellular release, therapeutic index, and bystander activity. Suppliers describe Gly-Gly-Phe-Gly as a linker that can be used in ADC synthesis and as a peptide spacer for Doxorubicin conjugates. The GGFG sequence is particularly relevant to protease-cleavable linker design. In many ADC platforms, peptide linkers are designed to be cleaved by lysosomal enzymes after antibody internalization. After the ADC binds to its target antigen and enters the tumor cell, intracellular proteases can process the linker and release the active payload. A protease-cleavable linker provides a mechanism for selective intracellular activation. This is especially important for potent cytotoxic payloads because uncontrolled release in plasma may cause off-target toxicity. By using peptide linkers such as Gly-Gly-Phe-Gly, researchers can design ADCs that remain relatively stable in circulation but become activated after internalization into antigen-positive cells. Gly-Gly-Phe-Gly and Puxitatug Samrotecan Gly-Gly-Phe-Gly is also associated with the synthesis of Puxitatug samrotecan (AZD8205), an antibody-drug conjugate. Product information describes Gly-Gly-Phe-Gly as an ADC linker that can be used to synthesize ADCs such as Puxitatug samrotecan. Puxitatug samrotecan drug-linker is described as a drug-linker conjugate for ADC synthesis, containing a topoisomerase I inhibitor and a linker. This connection highlights the growing importance of peptide linkers in next-generation ADC development. Topoisomerase I inhibitor payloads have become highly important in modern ADC research because they can provide strong cytotoxic activity and may support bystander killing when released in the tumor microenvironment. In such ADCs, the linker must balance stability with efficient payload liberation. Peptide spacer design is therefore central to the pharmacological behavior of these conjugates. For SEO and product-page use, it is accurate to position Gly-Gly-Phe-Gly as a peptide spacer and ADC linker intermediate relevant to Puxitatug samrotecan-related ADC synthesis. However, it is better to avoid claiming that Gly-Gly-Phe-Gly alone determines the activity of Puxitatug samrotecan. The biological performance of an ADC depends on the antibody target, drug-to-antibody ratio, payload structure, conjugation site, linker chemistry, tumor antigen expression, and cellular internalization pathway. Importance of Peptide Spacers in Drug Conjugates Peptide spacers are widely studied because they can improve the functional performance of drug conjugates. A spacer can separate a bulky carrier from a small-molecule drug, reduce steric hindrance, and provide an enzymatically responsive region. In polymer-drug conjugates, peptide spacers can affect drug release from macromolecular carriers. In ADCs, they can determine whether the payload is released efficiently after internalization. Gly-Gly-Phe-Gly is valuable because it offers a compact peptide sequence that can be integrated into conjugation systems. Its glycine residues provide flexibility, while phenylalanine may contribute to protease recognition or linker-substrate interaction. The short sequence also minimizes unnecessary molecular weight addition, which can be advantageous when researchers are optimizing drug loading, solubility, and conjugate homogeneity. In cancer research, this is particularly important. Drug conjugates are often designed to exploit tumor-associated features such as enhanced uptake, antigen expression, lysosomal processing, and altered protease activity. A well-designed linker helps ensure that the cytotoxic payload is delivered to the desired site and released under the right conditions. Research Applications Gly-Gly-Phe-Gly can be used in several research areas related to drug delivery and conjugate design. In Doxorubicin prodrug research, it can serve as a peptide spacer between Doxorubicin and a carrier molecule. Researchers may use it to study how peptide sequence affects drug release, antitumor activity, and conjugate stability. In ADC synthesis, Gly-Gly-Phe-Gly can be used as part of linker development workflows for constructing antibody-drug conjugates. It may be incorporated into cleavable linker systems designed for intracellular payload release. In macromolecular drug delivery, Gly-Gly-Phe-Gly can be evaluated as a spacer in polymer-drug conjugates, peptide-drug conjugates, and carrier-based prodrug systems. In structure-activity relationship studies, researchers may compare Gly-Gly-Phe-Gly with other peptide spacers to evaluate how sequence length, hydrophobicity, flexibility, and enzyme sensitivity influence drug release behavior. In ADC payload-linker optimization, Gly-Gly-Phe-Gly may be studied as part of linker-payload systems involving highly potent cytotoxic agents, including topoisomerase I inhibitor-based drug-linkers. Research Considerations When using Gly-Gly-Phe-Gly in conjugate design, researchers should carefully evaluate linker stability and cleavage behavior. A useful peptide spacer must maintain sufficient stability during synthesis, purification, formulation, and circulation. At the same time, it should enable efficient drug release in the desired biological compartment. Solubility is another important consideration. Gly-Gly-Phe-Gly is reported to be soluble in DMSO at high concentration in supplier data, which may be useful for preparing stock solutions during experimental workflows. However, solubility in final conjugation buffers may depend on concentration, pH, counterions, and the chemical groups attached to the peptide. Analytical characterization is also essential. Conjugates containing Gly-Gly-Phe-Gly should be evaluated by appropriate methods such as HPLC, LC-MS, MALDI-TOF MS, SDS-PAGE for antibody conjugates, drug-to-antibody ratio analysis, stability testing, enzyme cleavage assays, and in vitro cytotoxicity assays. Future Research Directions Current research in ADCs and polymer-drug conjugates is moving toward more precise linker engineering. Instead of using generic linkers, researchers increasingly design linkers for specific payloads, targets, tumor types, and intracellular release pathways. Peptide spacers such as Gly-Gly-Phe-Gly are important in this process because they provide tunable biological responsiveness. Future studies may focus on comparing Gly-Gly-Phe-Gly with other cleavable peptide sequences, optimizing its use with different cytotoxic payloads, and evaluating its performance in next-generation ADC platforms. In Doxorubicin conjugates, continued research may explore how Gly-Gly-Phe-Gly affects drug release kinetics, tumor accumulation, and toxicity profiles. In ADC research, it may remain useful as part of linker-payload systems designed for controlled intracellular activation. Conclusion Gly-Gly-Phe-Gly is a short peptide spacer and ADC linker intermediate with important applications in drug conjugate research. It can be applied to Doxorubicin conjugates and used in ADC synthesis, including systems related to Puxitatug samrotecan (AZD8205). Its GGFG sequence provides a compact peptide spacer structure that can support controlled drug release, linker-payload construction, and conjugate optimization. As research in targeted cancer therapy continues to advance, linker selection remains a critical factor in determining the success of ADCs and macromolecular prodrugs. Gly-Gly-Phe-Gly offers researchers a practical peptide spacer for studying drug release, conjugation efficiency, and linker-dependent biological performance in anticancer drug delivery systems.
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