Mc-Gly-Gly-Phe-Gly-PAB-OH TFA

Product Name: Mc-Gly-Gly-Phe-Gly-PAB-OH TFA

Sequence: GGFG

Purity: 95%

Form: White to off-white Solid

Storage : Sealed storage, away from moisture and light

CHEMICAl FORMULA: C34H39F3N6O10

SMILES: C1=CC=C(C=C1)C[C@@H](C(=O)NCC(=O)NC2=CC=C(C=C2)CO)NC(=O)CNC(=O)CNC(=O)CCCCCN3C(=O)C=CC3=O.C(=O)(C(F)(F)F)O

IUPACNAME: 6-(2,5-dioxopyrrol-1-yl)-N-[2-[[2-[[(2S)-1-[[2-[4-(hydroxymethyl)anilino]-2-oxoethyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]hexanamide;2,2,2-trifluoroacetic acid

INCHIKEY: DOTXLPVUMXESLK-UQIIZPHYSA-N

INCHI: InChI=1S/C32H38N6O8.C2HF3O2/c39-21-23-10-12-24(13-11-23)36-28(42)20-35-32(46)25(17-22-7-3-1-4-8-22)37-29(43)19-34-27(41)18-33-26(40)9-5-2-6-16-38-30(44)14-15-31(38)45;3-2(4,5)1(6)7/h1,3-4,7-8,10-15,25,39H,2,5-6,9,16-21H2,(H,33,40)(H,34,41)(H,35,46)(H,36,42)(H,37,43);(H,6,7)/t25-;/m0./s1

Molar Mass: 748.70

Application: Mc-Gly-Gly-Phe-Gly-PAB-OH TFA, also known as Mc-GGFG-PAB-OH TFA, is a cleavable ADC linker designed for antibody-drug conjugate research and synthesis. It contains a maleimidocaproyl group for thiol-based antibody conjugation, a Gly-Gly-Phe-Gly peptide sequence for protease-sensitive cleavage, and a PAB spacer that supports efficient payload release after enzymatic processing. The TFA salt form is suitable for peptide synthesis and bioconjugation workflows. Mc-GGFG-PAB-OH TFA is widely used in ADC linker development, targeted drug delivery studies, payload release evaluation, and medicinal chemistry research focused on protease-cleavable antibody-drug conjugates.

Current Research: Overview Mc-Gly-Gly-Phe-Gly-PAB-OH TFA, also known as Mc-GGFG-PAB-OH TFA, is a cleavable antibody-drug conjugate (ADC) linker used in the development and synthesis of ADC-related molecules. It contains three important linker design elements: a maleimidocaproyl (Mc) group, a Gly-Gly-Phe-Gly (GGFG) peptide sequence, and a PAB-OH self-immolative spacer. Product references describe Mc-Gly-Gly-Phe-Gly-PAB-OH TFA as a cleavable ADC linker used for antibody-drug conjugates. ADC linkers are central to the design of targeted anticancer therapeutics. An ADC typically consists of three major components: a monoclonal antibody, a linker, and a cytotoxic payload. The antibody provides tumor-associated antigen recognition, the payload provides cell-killing activity, and the linker controls how the payload is attached, transported, and released. Because of this role, linker chemistry strongly influences ADC stability, pharmacokinetics, payload release, therapeutic index, and off-target toxicity. Mc-GGFG-PAB-OH TFA is especially relevant in research requiring a protease-sensitive peptide linker combined with a self-immolative spacer. The GGFG peptide motif can serve as the cleavable region, while the PAB group can assist payload release after enzymatic processing. This makes Mc-Gly-Gly-Phe-Gly-PAB-OH TFA a useful intermediate for constructing ADC linker-payload systems and for studying controlled drug release in targeted cancer therapy research. Structural Design of Mc-GGFG-PAB-OH TFA The structure of Mc-Gly-Gly-Phe-Gly-PAB-OH TFA is modular. Each part contributes to its function in ADC synthesis. The Mc group, or maleimidocaproyl group, is commonly used for conjugation to thiol-containing groups, especially cysteine residues on antibodies or engineered proteins. Maleimide chemistry is widely used in ADC development because it allows covalent attachment of linker-payload structures to reduced interchain cysteines or site-specific cysteine residues on antibodies. This conjugation handle makes Mc-GGFG-PAB-OH TFA suitable for antibody-linker assembly strategies. The GGFG peptide sequence is composed of glycine-glycine-phenylalanine-glycine. Peptide linkers are often used in ADCs because they can be designed for enzymatic cleavage after internalization into tumor cells. In ADC research, cleavable linkers are intended to remain sufficiently stable in circulation but release the payload efficiently after the ADC enters target cells and traffics to intracellular compartments such as lysosomes. ADC linker reviews emphasize that cleavable and non-cleavable linker selection is a major determinant of ADC stability, efficacy, and toxicity. The PAB-OH group is related to p-aminobenzyl alcohol, a self-immolative spacer. Self-immolative spacers are used in ADC linker design because they can undergo spontaneous breakdown after a triggering event, helping release the active payload from the linker system. PAB-type spacers are widely discussed as self-immolative components in ADC linker technology. Together, these structural elements make Mc-GGFG-PAB-OH TFA a functional building block for cleavable ADC linker development. Role of the GGFG Peptide Linker The Gly-Gly-Phe-Gly sequence is a short peptide spacer that can be incorporated into drug conjugates and ADC linker systems. In Mc-GGFG-PAB-OH TFA, this tetrapeptide segment provides the cleavable peptide portion of the linker. Its sequence includes flexible glycine residues and one phenylalanine residue, giving the linker a balance of conformational flexibility and hydrophobic/aromatic character. Peptide linkers are widely used in ADC design because intracellular proteases can recognize and cleave specific peptide sequences. After an ADC binds to a target antigen on the tumor cell surface, it can be internalized and trafficked to lysosomal compartments. In this environment, proteases may cleave the peptide linker, initiating release of the cytotoxic payload. Cathepsin-sensitive peptide linkers commonly use protease-cleavable motifs together with self-immolative spacer groups such as PABC or related PAB-type structures. For SEO product-page wording, it is accurate to describe Mc-GGFG-PAB-OH TFA as a cleavable ADC linker containing a GGFG peptide spacer. However, its exact cleavage behavior should be experimentally validated in each linker-payload and antibody context. ADC linker performance depends not only on the peptide sequence but also on antibody conjugation site, payload structure, drug-to-antibody ratio, hydrophobicity, antigen internalization, lysosomal trafficking, and plasma stability. Importance of PAB-OH as a Self-Immolative Spacer The PAB-OH component is important because many cytotoxic payloads require clean release from the linker to achieve full activity. In ADC systems, enzymatic cleavage of the peptide sequence alone may not always directly release the free active drug. A self-immolative spacer can solve this problem by connecting the cleavable peptide to the payload and then decomposing after the peptide is removed. The general mechanism involves a trigger event, such as protease-mediated cleavage of the peptide segment. Once the trigger occurs, the PAB-type spacer undergoes a self-immolative cascade, allowing the payload to be released from the linker structure. This design is especially useful when researchers want the ADC to remain stable during systemic circulation but release the active agent inside tumor cells. In Mc-GGFG-PAB-OH TFA, the PAB-OH unit therefore supports controlled release design. It helps bridge the cleavable GGFG peptide and a downstream payload or functional group. This makes Mc-GGFG-PAB-OH TFA relevant to linker-payload synthesis, ADC payload release studies, and optimization of cleavable ADC platforms. Application in Antibody-Drug Conjugate Research Mc-Gly-Gly-Phe-Gly-PAB-OH TFA is used in ADC research as a linker intermediate or linker building block. It can support the construction of ADCs in which a cytotoxic payload is attached to an antibody through a cleavable peptide-spacer system. The central research objective of this type of linker is to improve the therapeutic index of highly potent drugs. Many ADC payloads are too toxic for systemic administration as free drugs. By attaching them to antibodies through carefully designed linkers, researchers aim to concentrate payload delivery in antigen-positive tumor cells while reducing nonspecific exposure to healthy tissues. In this context, Mc-GGFG-PAB-OH TFA may be used in studies involving: Cleavable ADC linker synthesis, where the GGFG peptide sequence and PAB spacer are incorporated into linker-payload structures. Antibody conjugation chemistry, where the Mc maleimide group can support thiol-based attachment to antibody cysteine residues. Payload release studies, where researchers evaluate how efficiently the peptide-spacer system releases active payload under enzymatic or lysosomal conditions. ADC stability testing, where linker behavior is examined in plasma, buffer systems, cell culture media, or intracellular mimic conditions. Structure-activity relationship research, where Mc-GGFG-PAB-OH TFA may be compared with other peptide linkers such as Val-Cit, Val-Ala, or other GGFG-based structures. Cleavable Linkers and ADC Performance The linker is often one of the most important variables in ADC development. A linker that is too unstable may release payload prematurely in circulation, increasing systemic toxicity. A linker that is too stable may prevent efficient payload release inside tumor cells, reducing antitumor activity. Therefore, successful ADC linker design requires a careful balance between circulation stability and intracellular release efficiency. Cleavable peptide linkers are attractive because they can exploit biological differences between plasma and intracellular compartments. Tumor cells that internalize ADCs can route them to lysosomes, where proteases and acidic conditions support linker processing. This allows payload release to occur preferentially after cellular uptake. Mc-GGFG-PAB-OH TFA fits into this design strategy. The GGFG peptide motif provides a cleavable segment, while the PAB-OH spacer supports downstream release chemistry. The Mc group provides a conjugation handle for antibody attachment. This modular arrangement reflects a common design logic in modern ADC linker chemistry: one component for antibody attachment, one component for biological cleavage, and one component for payload release. Research Considerations Researchers using Mc-Gly-Gly-Phe-Gly-PAB-OH TFA should consider several experimental factors. First, maleimide conjugation chemistry can influence ADC stability. Maleimide-thiol linkages are widely used, but their stability may depend on conjugation conditions, antibody engineering, buffer composition, and downstream stabilization strategies. Second, peptide cleavage must be validated experimentally. Although GGFG is used as a cleavable peptide motif, the actual release profile depends on the complete linker-payload structure and the biological system being tested. Third, PAB spacer behavior depends on payload attachment chemistry. Self-immolation is most useful when the spacer is properly connected to a payload through a linkage that can release the active drug after trigger cleavage. Fourth, hydrophobicity and aggregation risk should be monitored. ADC linker-payload structures can affect antibody aggregation, drug-to-antibody ratio distribution, solubility, and pharmacokinetics. Fifth, analytical characterization is essential. Researchers may use LC-MS, HPLC, peptide mapping, hydrophobic interaction chromatography, size-exclusion chromatography, SDS-PAGE, and cell-based cytotoxicity assays to evaluate linker-payload identity, conjugation efficiency, ADC homogeneity, stability, and activity. Future Research Directions Current ADC research is moving toward more precise and tunable linker systems. While early ADCs often relied on a limited number of linker chemistries, modern ADC development increasingly optimizes the linker for a specific antibody, antigen, tumor type, payload, and release mechanism. Linkers such as Mc-GGFG-PAB-OH TFA are relevant to this trend because they provide a modular structure that can be adapted for controlled payload release. Future studies may continue to explore GGFG-based peptide linkers in combination with different payload classes, including topoisomerase inhibitors, tubulin inhibitors, DNA-damaging agents, and immune-modulating payloads. Researchers may also investigate how GGFG-PAB systems compare with other cleavable linkers in terms of plasma stability, intracellular release rate, bystander effect, and therapeutic window. As ADCs become more sophisticated, linker design will remain a key determinant of clinical and preclinical success. Mc-Gly-Gly-Phe-Gly-PAB-OH TFA offers a useful research tool for studying the relationship between peptide cleavage, self-immolation, conjugation chemistry, and payload release. Conclusion Mc-Gly-Gly-Phe-Gly-PAB-OH TFA, or Mc-GGFG-PAB-OH TFA, is a cleavable ADC linker used in antibody-drug conjugate research. Its structure combines a maleimidocaproyl conjugation group, a GGFG peptide cleavage motif, and a PAB-OH self-immolative spacer. This modular design makes it useful for ADC linker-payload synthesis and controlled release studies. In current ADC research, Mc-GGFG-PAB-OH TFA is valuable because it supports three essential linker functions: antibody attachment, enzymatic cleavage, and payload release. By enabling targeted delivery and intracellular activation, cleavable ADC linkers like Mc-GGFG-PAB-OH TFA contribute to the development of more selective and effective anticancer drug conjugates.