Mca-YVADAPK(Dnp)

Product Name:Mca-YVADAPK(Dnp)

Form:TFA salt

Purity:95%

Storage:2-8 degree Celsius

Cas No:189696-01-3

Molar Mass:1305.4

Chemical Formula:C60H80N12O21

IUPAC Name:(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-3-carboxy-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[[2-(7-methoxy-2-oxochromen-4-yl)acetyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]propanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-6-(2,4-dinitroanilino)hexanoic acid

SMILES:C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCNC2=C(C=C(C=C2)[N+](=O)[O-])[N+](=O)[O-])C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC3=CC=C(C=C3)O)NC(=O)CC4=CC(=O)OC5=C4C=CC(=C5)OC

InChIKey:XLXKHBNLWUCNOC-XUFBPUFYSA-N

InChI:InChI=1S/C53H64N10O19/c1-27(2)46(60-49(71)38(21-30-11-14-33(64)15-12-30)57-43(65)22-31-23-45(68)82-42-25-34(81-5)16-17-35(31)42)51(73)55-28(3)47(69)59-39(26-44(66)67)48(70)56-29(4)52(74)61-20-8-10-40(61)50(72)58-37(53(75)76)9-6-7-19-54-36-18-13-32(62(77)78)24-41(36)63(79)80/h11-18,23-25,27-29,37-40,46,54,64H,6-10,19-22,26H2,1-5H3,(H,55,73)(H,56,70)(H,57,65)(H,58,72)(H,59,69)(H,60,71)(H,66,67)(H,75,76)/t28-,29-,37-,38-,39-,40-,46-/m0/s1

Sequence:Mca-Tyr-Val-Ala-Asp-Ala-Pro-Lys(DNP)

Application:Mca-YVADAPK(Dnp) is a fluorogenic peptide substrate designed for caspase-1 (ICE) activity assays. It features an Mca (7-methoxycoumarin-4-yl) fluorophore at the N-terminus and a Dnp (2,4-dinitrophenyl) quencher at the C-terminus, enabling FRET-based detection. Upon enzymatic cleavage at the YVAD sequence, fluorescence is released, providing a sensitive method to measure caspase-1 activity in apoptosis and inflammation studies. This substrate is widely used in drug discovery, screening of caspase inhibitors, and cellular response investigations in inflammatory and immune signaling pathways. It is a valuable tool in cancer, neurodegenerative disease, and inflammatory research, supporting high-throughput screening and mechanistic enzymology studies.

Current Research:

Caspase-1 plays a central role in inflammatory processes, particularly in pyroptosis and the maturation of pro-inflammatory cytokines such as IL-1β and IL-18. The fluorogenic substrate Mca-YVADAPK(Dnp) has become a crucial tool for researchers studying caspase-1 activation and inhibition in the context of inflammatory and immune-related diseases. This substrate allows for real-time, high-throughput detection of caspase-1 activity, making it highly useful in drug discovery and disease mechanism studies.

1. Role in Inflammasome Research
   The inflammasome is a multiprotein complex that activates caspase-1, leading to the processing of IL-1β and IL-18, which are key mediators of inflammation. Recent studies have employed Mca-YVADAPK(Dnp) to monitor caspase-1 activity in response to inflammasome activation in diseases such as autoimmune disorders, sepsis, and metabolic syndrome. Researchers have used this substrate to evaluate caspase-1 inhibitors as potential therapeutics, including small molecules targeting the NLRP3 inflammasome pathway.
2. Application in Neuroinflammation and Neurodegenerative Diseases
   Caspase-1-mediated neuroinflammation has been implicated in Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. The use of Mca-YVADAPK(Dnp) has facilitated the study of caspase-1 activation in glial cells and neurons, allowing researchers to track inflammasome-induced cell death in neurodegenerative conditions. In Alzheimer’s research, this substrate has helped confirm that β-amyloid peptides and tau aggregates can trigger caspase-1 activity, leading to inflammation-driven neurotoxicity.
3. Cancer and Immune Checkpoints
   The role of caspase-1 in cancer is complex, as it can contribute to both tumor suppression and tumor progression. Caspase-1 activation can induce pyroptosis, a form of programmed cell death, which has been linked to anti-tumor immune responses. On the other hand, excessive caspase-1 activity in the tumor microenvironment may promote chronic inflammation and immune evasion. Studies utilizing Mca-YVADAPK(Dnp) have identified novel caspase-1 inhibitors as potential cancer therapeutics, particularly in colorectal cancer and hematological malignancies.
4. Drug Discovery and Inhibitor Screening
   Pharmaceutical research has extensively employed Mca-YVADAPK(Dnp) in high-throughput screening of caspase-1 inhibitors. Novel small molecules that suppress IL-1β-driven inflammation are under investigation for conditions like rheumatoid arthritis, type 2 diabetes, and atherosclerosis. This substrate remains a key component in enzymatic assays evaluating drug candidates targeting inflammatory pathways.

In summary, Mca-YVADAPK(Dnp) is an essential tool for studying caspase-1 activity in inflammation, neurodegeneration, cancer, and metabolic diseases, reinforcing its value in biomedical research.