Product Name: Boc-Gly-Gly-Phe-Gly-OH TFA
Sequence: Boc-GGFG
Purity: 98%
Form: White to off-white Solid
Storage : Sealed storage, away from moisture
CAS.NO.: 2450273-39-7
CHEMICAl FORMULA: C22H29F3N4O9
Molar Mass: 550.48
SMILES: CC(C)(C)OC(=O)NCC(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)O.C(=O)(C(F)(F)F)O
IUPACNAME: 2-[[(2S)-2-[[2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]acetic acid;2,2,2-trifluoroacetic acid
INCHIKEY: RXCXUMYQOKOAGZ-UQKRIMTDSA-N
INCHI: InChI=1S/C20H28N4O7.C2HF3O2/c1-20(2,3)31-19(30)23-10-15(25)21-11-16(26)24-14(18(29)22-12-17(27)28)9-13-7-5-4-6-8-13;3-2(4,5)1(6)7/h4-8,14H,9-12H2,1-3H3,(H,21,25)(H,22,29)(H,23,30)(H,24,26)(H,27,28);(H,6,7)/t14-;/m0./s1
Application: Boc-Gly-Gly-Phe-Gly-OH TFA is an N- and C-protected tetrapeptide linker used in antibody-drug conjugate (ADC) research. This GGFG sequence functions as a protease-cleavable linker, enabling controlled payload release after enzymatic processing in target cells or tumor-associated environments. The Boc-protected structure supports peptide synthesis, linker assembly, and incorporation into drug-linker intermediates. Boc-Gly-Gly-Phe-Gly-OH TFA is valuable for studying linker stability, protease-sensitive cleavage, payload release mechanisms, and ADC design strategies. It is widely used in medicinal chemistry, bioconjugation research, peptide synthesis, and development of targeted antibody-drug conjugates for cancer research.
Current Research: Overview Boc-Gly-Gly-Phe-Gly-OH TFA, also known as Boc-GGFG-OH TFA, is an N- and C-protected tetrapeptide derivative based on the sequence Gly-Gly-Phe-Gly. It is described as a self-assembling protected tetrapeptide and a protease-cleavable linker used in antibody-drug conjugate (ADC) research. Because it contains the GGFG peptide motif, Boc-Gly-Gly-Phe-Gly-OH TFA is relevant to studies involving peptide linker design, enzymatic cleavage, payload release, linker-payload synthesis, and targeted cancer drug delivery. In ADC development, the linker is a critical structural component. An ADC typically contains a monoclonal antibody, a chemical linker, and a cytotoxic payload. The antibody directs the conjugate toward tumor-associated antigens, while the payload provides cell-killing activity. The linker controls how the payload is attached, how stable the ADC remains in circulation, and how efficiently the active drug is released after internalization into target cells. Boc-Gly-Gly-Phe-Gly-OH TFA is useful as a peptide-linker building block because the GGFG sequence can be incorporated into cleavable ADC linker systems. The compound is not a complete ADC by itself. Instead, it is a protected peptide intermediate that can support the synthesis of more complex linker-payload structures. Its value lies in its short peptide sequence, protected termini, potential self-assembly behavior, and applicability in protease-responsive linker design. Structural Features of Boc-Gly-Gly-Phe-Gly-OH TFA Boc-Gly-Gly-Phe-Gly-OH TFA contains four amino acid residues: Gly – glycine Gly – glycine Phe – phenylalanine Gly – glycine The N-terminus is protected with a Boc group, or tert-butyloxycarbonyl group. Boc protection is commonly used in peptide and organic synthesis to prevent unwanted reaction at the amino terminus. This allows researchers to control stepwise modification and coupling during linker synthesis. The C-terminal region is present as a carboxylic acid form, represented by -OH, and the compound is supplied as a TFA salt. The trifluoroacetate salt form is common for synthetic peptides purified by reverse-phase HPLC and may influence handling, solubility, and storage. The GGFG tetrapeptide sequence has several notable features. Glycine residues provide flexibility and minimal steric bulk, while phenylalanine introduces an aromatic hydrophobic side chain. This combination gives the linker a balance of conformational mobility and hydrophobic character. In linker design, such a sequence may help improve enzyme accessibility, spacing, and controlled release behavior. Self-Assembly of N- and C-Protected Tetrapeptides Boc-Gly-Gly-Phe-Gly-OH TFA is described as a self-assembly of N- and C-protected tetrapeptide. Self-assembling peptides are important in biomaterials and supramolecular chemistry because small peptide molecules can organize into higher-order structures through noncovalent interactions. These interactions may include hydrogen bonding, hydrophobic association, π-π stacking from aromatic residues, and electrostatic effects. The phenylalanine residue in Boc-GGFG-OH can contribute to hydrophobic and aromatic interactions, while the peptide backbone can participate in hydrogen bonding. The Boc protecting group may also influence molecular packing and hydrophobic association. These structural features can support peptide self-assembly under appropriate conditions. Self-assembly behavior is relevant not only to biomaterials research but also to linker and conjugate design. Peptide aggregation, molecular packing, and hydrophobic interactions can influence solubility, purification, conjugation efficiency, and biological behavior. For ADC linker development, understanding the self-assembly or aggregation tendency of peptide-linker intermediates is useful because linker-payload hydrophobicity can affect ADC homogeneity and pharmacokinetics. Role as a Protease-Cleavable Linker Boc-Gly-Gly-Phe-Gly-OH TFA is described as a protease-cleavable linker for ADC research. Protease-cleavable linkers are designed to remain sufficiently stable outside target cells and then undergo cleavage after the ADC is internalized and transported to protease-rich intracellular compartments, such as lysosomes. The GGFG motif can serve as a peptide spacer or cleavable sequence in drug conjugate systems. In an ADC, a protease-cleavable peptide linker may be placed between the antibody attachment site and the cytotoxic payload. After antibody binding and internalization, intracellular proteases can process the peptide sequence. This cleavage can trigger downstream payload release, especially when the peptide is combined with a self-immolative spacer such as PAB or PABC. This mechanism is central to many ADC designs. A cleavable linker can help concentrate payload release inside antigen-positive tumor cells, reducing premature drug release in circulation. However, cleavage behavior depends on the complete linker-payload architecture, steric accessibility, protease expression, and intracellular trafficking pathway. Therefore, Boc-Gly-Gly-Phe-Gly-OH TFA should be described as a protease-cleavable linker building block rather than as a complete release system on its own. Importance in ADC Linker Design ADC linker design must balance two competing needs: systemic stability and intracellular release. If a linker is too labile, the payload may be released prematurely in blood or normal tissues, increasing toxicity. If the linker is too stable, the payload may not be released efficiently inside tumor cells, reducing anticancer activity. Boc-Gly-Gly-Phe-Gly-OH TFA contributes to this design space by providing a short peptide motif that can be incorporated into cleavable linkers. Its Gly-Gly-Phe-Gly sequence may be used in linker screening studies to evaluate how peptide composition affects cleavage, release kinetics, solubility, and conjugate performance. Compared with non-cleavable linkers, protease-cleavable linkers can provide more direct payload release after cellular uptake. Compared with some other peptide sequences, GGFG offers a compact structure with both flexible glycine residues and an aromatic phenylalanine residue. These properties may influence protease recognition and linker behavior in biological systems. Applications in Antibody-Drug Conjugate Research Boc-Gly-Gly-Phe-Gly-OH TFA can be used in several ADC-related research workflows. In linker-payload synthesis, it may serve as a protected peptide intermediate for building cleavable drug-linker structures. In protease-cleavable linker development, the GGFG sequence may be incorporated into ADC linkers designed for intracellular processing. In payload release studies, Boc-GGFG-derived linkers may be used to study enzyme-triggered cleavage and downstream drug liberation. In structure-activity relationship research, scientists may compare GGFG-containing linkers with other peptide motifs such as Val-Cit, Val-Ala, Gly-Phe-Leu-Gly, or Ala-Ala-Asn to determine how sequence affects ADC performance. In cancer research, ADCs containing cleavable peptide linkers are studied for targeted delivery of highly potent cytotoxic agents to tumor cells. In bioconjugation chemistry, protected tetrapeptide intermediates such as Boc-Gly-Gly-Phe-Gly-OH TFA may support modular construction of peptide-drug conjugates, antibody conjugates, or ligand-drug conjugates. Relevance to Cancer Research ADC technology is one of the most important targeted delivery approaches in cancer research. Many cytotoxic drugs are highly potent but too toxic to administer systemically in unconjugated form. ADCs aim to improve selectivity by attaching these payloads to antibodies that recognize tumor-associated antigens. The linker is essential in this strategy. It must protect the payload during circulation and enable release after tumor-cell uptake. Protease-cleavable peptide linkers are particularly useful because they exploit intracellular enzymatic processing. Boc-Gly-Gly-Phe-Gly-OH TFA supports this research area as a tetrapeptide linker intermediate for building protease-responsive ADC systems. GGFG-containing linkers may be relevant to ADCs carrying different payload classes, including topoisomerase inhibitors, tubulin inhibitors, DNA-damaging agents, and other cytotoxic molecules. The final biological performance depends on the full ADC design, including antibody target, payload potency, drug-to-antibody ratio, conjugation chemistry, linker stability, and antigen internalization rate. Research Considerations Researchers using Boc-Gly-Gly-Phe-Gly-OH TFA should consider several factors. First, it is a protected peptide intermediate, not the final ADC. Its performance depends on how it is modified and incorporated into the full linker-payload structure. Second, the Boc protecting group must be managed carefully. Deprotection conditions should be compatible with downstream functional groups and should not degrade sensitive intermediates. Third, the C-terminal carboxylic acid may require activation before coupling to amine-containing spacers, payloads, or self-immolative groups. Coupling reagents and reaction conditions should be optimized to minimize racemization, hydrolysis, and side reactions. Fourth, the GGFG sequence may influence solubility and self-assembly. The phenylalanine residue and Boc group can increase hydrophobic character, which may affect purification, storage, and formulation. Fifth, protease cleavage should be validated experimentally. Enzymatic responsiveness depends on the final conjugate structure, not just the isolated tetrapeptide sequence. Analytical methods such as HPLC, LC-MS, NMR, MALDI-TOF MS, peptide mapping, enzyme cleavage assays, plasma stability testing, and cell-based cytotoxicity assays may be used to evaluate linker identity, purity, stability, and function. Future Research Directions As ADC technology advances, linker chemistry is becoming increasingly sophisticated. Researchers are optimizing peptide sequences, self-immolative spacers, hydrophilic modifiers, conjugation handles, and payload attachment strategies to improve the therapeutic index of ADC candidates. Boc-Gly-Gly-Phe-Gly-OH TFA may remain useful as a modular tetrapeptide building block for GGFG-based cleavable linkers. Future studies may examine how N- and C-protected GGFG derivatives self-assemble, how their hydrophobicity affects linker-payload behavior, and how GGFG-containing linkers compare with other protease-cleavable sequences. The compound may also be useful beyond ADCs, including peptide-drug conjugates, ligand-drug conjugates, enzyme-responsive probes, and self-assembling peptide materials. Its combination of peptide cleavage potential and self-assembly behavior makes it relevant to both chemical biology and biomaterials research. Conclusion Boc-Gly-Gly-Phe-Gly-OH TFA is an N- and C-protected tetrapeptide derivative based on the GGFG sequence. It is described as a self-assembling protected tetrapeptide and a protease-cleavable linker used in antibody-drug conjugate research. Its structure combines a Boc-protected N-terminus, a flexible Gly-Gly-Phe-Gly peptide motif, and a C-terminal carboxylic acid in TFA salt form. In ADC research, Boc-Gly-Gly-Phe-Gly-OH TFA can support the synthesis of cleavable linker-payload systems designed for intracellular protease-mediated drug release. As targeted cancer therapy and bioconjugation technologies continue to evolve, Boc-Gly-Gly-Phe-Gly-OH TFA provides a useful peptide-linker building block for ADC linker development, protease-responsive conjugate synthesis, and studies of protected tetrapeptide self-assembly.
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