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

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

Sequence: GGFG

Purity: 98%

Form: White to yellow Solid

Storage : Sealed storage, away from moisture

CAS.NO.: 2632342-05-1

CHEMICAl FORMULA: C32H38N6O8

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

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

INCHIKEY: CTYXSHFYZMWMPD-VWLOTQADSA-N

INCHI: InChI=1S/C32H38N6O8/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/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)/t25-/m0/s1

Molarmass: 634.68

Application: Mc-Gly-Gly-Phe-Gly-PAB-OH, also known as Mc-GGFG-PAB-OH, is a cleavable ADC linker designed for antibody-drug conjugate research. It contains a maleimidocaproyl (Mc) group for thiol-based conjugation, a Gly-Gly-Phe-Gly peptide sequence for protease-sensitive cleavage, and a PAB spacer that supports payload release after enzymatic processing. This linker is commonly used to connect cytotoxic payloads to antibodies in targeted drug delivery studies. Mc-GGFG-PAB-OH is valuable for ADC synthesis, linker stability evaluation, payload release mechanism studies, and medicinal chemistry research focused on protease-cleavable linker systems and antibody-mediated cancer therapy development.

Current Research: Mc-Gly-Gly-Phe-Gly-PAB-OH, commonly abbreviated Mc-GGFG-PAB-OH, is a cleavable antibody–drug conjugate linker intermediate used in ADC linker design, payload release studies, and bioconjugation research. The structure contains a maleimidocaproyl group, a Gly-Gly-Phe-Gly peptide segment, and a PAB self-immolative spacer. This combination makes the linker useful for constructing antibody–drug conjugates and related targeted delivery systems in which payload release is designed to occur after protease-mediated cleavage. A major application of Mc-GGFG-PAB-OH is ADC synthesis research. Antibody–drug conjugates generally consist of a targeting antibody, a chemical linker, and a biologically active payload. The linker must perform several functions at once: it must connect the payload to the antibody, preserve stability during handling and circulation-like conditions, allow efficient conjugation, and release the payload under intended intracellular or disease-associated conditions. Mc-GGFG-PAB-OH provides a modular linker architecture for studying this balance between stability and controlled release. The Mc group, or maleimidocaproyl moiety, is widely used in cysteine-directed conjugation chemistry. Maleimide groups can react with thiol groups on reduced antibody cysteines or engineered cysteine residues, forming thioether-linked conjugates. This makes Mc-GGFG-PAB-OH valuable in workflows where researchers need to attach a linker-payload unit to antibodies, antibody fragments, proteins, peptides, or thiol-containing carriers. The caproyl spacer provides distance between the maleimide conjugation site and the cleavable peptide region, which can help reduce steric constraints. The Gly-Gly-Phe-Gly sequence is a protease-cleavable peptide motif. In ADC research, peptide linkers are often designed to be cleaved after internalization into lysosomal or protease-rich compartments. The GGFG segment can be studied for its susceptibility to cathepsins or related proteases, depending on assay conditions and complete conjugate structure. This peptide sequence helps researchers investigate enzyme-responsive drug release and compare cleavage behavior with other commonly studied ADC motifs such as Val-Cit, Phe-Lys, Gly-Phe-Leu-Gly, or Ala-Ala-Asn. The PAB group, or para-aminobenzyl spacer, is an important self-immolative unit. After protease cleavage of the peptide linker, the PAB spacer can undergo self-immolation to release the attached payload in a more native or active form, depending on payload attachment chemistry. This design is frequently used when direct protease cleavage next to the payload would not efficiently release the desired molecule. In research workflows, Mc-GGFG-PAB-OH can therefore support studies of payload liberation, spacer fragmentation, linker stability, and release kinetics. Mc-GGFG-PAB-OH is also useful in linker–payload assembly. The terminal hydroxyl group can be further functionalized or converted into activated derivatives depending on synthetic strategy. Researchers may use the compound as an intermediate for attaching cytotoxic payloads, fluorescent probes, imaging agents, affinity tags, or other functional molecules. It can support synthesis of complete linker-payload constructs that are later conjugated to antibodies or targeting proteins through the maleimide group. Protease cleavage studies represent another major use. Researchers can incubate Mc-GGFG-PAB-containing constructs with purified proteases, lysosomal extracts, tumor cell lysates, plasma-like matrices, or intracellular enzyme preparations to evaluate cleavage sensitivity. LC-MS, HPLC, fluorescence release assays, and payload quantification can be used to measure linker degradation and payload release. Such experiments help determine whether the linker is stable in non-target conditions yet cleavable in intended biological environments. This linker is also relevant to targeted delivery platform development beyond classical ADCs. Mc-GGFG-PAB-OH-derived linkers may be adapted for antibody fragments, nanobodies, protein conjugates, peptide-targeted payloads, polymer–drug conjugates, nanoparticles, or other thiol-reactive delivery systems. The maleimide group provides a versatile conjugation handle, while the GGFG-PAB module supports protease-responsive release. In ADC optimization, linker hydrophobicity, aggregation risk, drug-to-antibody ratio, conjugation site, payload structure, and cleavage rate all affect final conjugate performance. Mc-GGFG-PAB-OH can be used in comparative linker studies to evaluate how the GGFG-PAB design influences conjugate stability, solubility, binding retention, internalization, lysosomal release, and payload activity. It may be compared with non-cleavable linkers or alternative cleavable linkers to define the most appropriate design for a specific payload and targeting antibody. Analytical characterization is important in workflows using Mc-GGFG-PAB-OH. Researchers typically confirm identity and purity by LC-MS, HPLC, and, where needed, NMR. For complete ADCs or linker-payload conjugates, additional analysis may include drug-to-antibody ratio, aggregation by SEC-HPLC, hydrophobic interaction chromatography, peptide mapping, free drug measurement, stability testing, and release-product identification. Recommended controls include non-cleavable linker analogs, Val-Cit-PAB comparators, GGFG linker variants without PAB, enzyme-free controls, heat-inactivated protease controls, plasma or serum stability assays, lysosomal extract cleavage assays, and LC-MS confirmation of released products. For conjugation workflows, reduced antibody-only, maleimide-only, payload-only, and unconjugated antibody controls are useful. Overall, Mc-Gly-Gly-Phe-Gly-PAB-OH is a valuable cleavable ADC linker intermediate for targeted delivery and bioconjugation research. It supports cysteine-directed conjugation, GGFG protease-cleavable linker design, PAB-mediated self-immolative payload release, antibody–drug conjugate synthesis, linker stability testing, protease release assays, linker–payload assembly, and development of next-generation ADC and peptide–drug conjugate platforms.