SMR8 Antibody

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Description

Introduction to S100A8 (MRP8) Antibody

S100A8 (MRP8) is a member of the S100 protein family, forming heterodimers with S100A9 (MRP14) as calprotectin. This protein plays dual roles:

  • Intracellular: Modulates leukocyte cytoskeleton dynamics, NADPH oxidase activation, and arachidonic acid metabolism .

  • Extracellular: Acts as a damage-associated molecular pattern (DAMP), promoting inflammation via Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER) .

Antibodies against S100A8 are critical for detecting its overexpression in inflammatory diseases (e.g., rheumatoid arthritis) and cancers (e.g., lung adenocarcinoma) .

Antibody Structure

  • Target Epitope: S100A8 antibodies typically bind to linear or conformational epitopes within the S100A8 protein. For example, the monoclonal antibody MAB4570 detects human S100A8 at ~11 kDa via western blot .

  • Format: Most are IgG-class monoclonal antibodies (e.g., Rabbit monoclonal [EPR3554] or Mouse IgG1) .

Mechanism of Action

FunctionMechanism
NeutralizationBlocks S100A8 interaction with TLR4/AGER, reducing pro-inflammatory signaling .
Diagnostic DetectionBinds soluble or tissue-bound S100A8 for immunohistochemistry (IHC) or ELISA .
Therapeutic PotentialReduces inflammation in murine models of autoimmune disease .

Key Studies

  • Hybridoma Generation: A 2023 study developed a high-affinity monoclonal anti-S100A8 antibody using recombinant S100A8 protein and hybridoma technology, enabling early diagnosis of inflammatory diseases .

  • Preclinical Models: Anti-S100A8 antibodies improved cognitive deficits in SAMP8 mice by mitigating β-amyloid toxicity .

Diagnostic Use

  • Cancer: S100A8 is overexpressed in lung cancer tissues, detectable via IHC in cytoplasmic and nuclear regions .

  • Inflammation: Serum calprotectin (S100A8/A9) serves as a biomarker for neutrophil activation in sepsis .

Therapeutic Potential

  • Autoimmunity: Antibodies blocking S100A8 reduce neutrophil extracellular trap (NET) formation, a driver of lupus nephritis .

  • Neurodegeneration: Anti-S100A8 antibodies restored memory retention in Alzheimer’s disease models by counteracting β-amyloid toxicity .

Challenges and Future Directions

  • Specificity: Cross-reactivity with S100A9 remains a concern; novel antibodies must validate selectivity .

  • Clinical Translation: No S100A8-targeted therapies are yet FDA-approved, though preclinical data support trials in inflammatory disorders .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M Phosphate Buffered Saline (PBS), pH 7.4
Form
Liquid
Lead Time
Made-to-order (14-16 weeks)
Synonyms
SMR8 antibody; At1g10690 antibody; T16B5.17Cyclin-dependent protein kinase inhibitor SMR8 antibody; Protein SIAMESE-RELATED 8 antibody
Target Names
SMR8
Uniprot No.

Target Background

Function
SMR8 Antibody is a probable cyclin-dependent protein kinase (CDK) inhibitor that functions as a repressor of mitosis in the endoreduplication cell cycle.
Database Links

KEGG: ath:AT1G10690

STRING: 3702.AT1G10690.1

UniGene: At.43217

Tissue Specificity
Expressed in the root vascular tissue.

Q&A

Here’s a structured collection of research-focused FAQs for SMR8 Antibody, synthesized from peer-reviewed methodologies and experimental frameworks:

Advanced Research Challenges

How to resolve contradictory binding data between SPR and BLI for SMR8?

  • Root cause analysis:

    • SPR measures solution-phase affinity (KD), while BLI assesses surface-immobilized interactions.

    • Check for avidity effects: SMR8’s bivalency may artificially enhance BLI signals .

  • Resolution workflow:

    • Repeat with Fab fragments

    • Compare under matched buffer conditions (pH 7.4, 150mM NaCl)

    • Validate with orthogonal methods (e.g., ITC) .

What computational strategies optimize SMR8’s CDR regions for enhanced neutralization?

  • Energy-based design:

    • Train conditional diffusion model on antibody-antigen co-structures

    • Apply residue-level decomposed energy optimization:

      • Attractive: VDW contacts <3Å

      • Repulsive: Clashes >1.5Å

  • Validation metrics:

    • ΔG improvement ≥2 kcal/mol vs wild-type

    • Epitope contact residues ≥15 (cryo-EM verification)

How to analyze SMR8’s immunogenicity risk in therapeutic development?

  • ADA assessment framework:

    TierAssay TypeDecision Threshold
    1Screening (ELISA)Signal ≥2× baseline
    2Confirmatory≥50% signal inhibition
    3NeutralizationIC50 shift ≥2-fold
  • Risk mitigation: Engineer Fc region with XPro mutation (IgG4 S228P) to reduce effector function .

Mechanistic Studies

What structural features enable SMR8’s broad neutralization capacity?

  • Cryo-EM findings:

    • Binds RBD in "up" conformation with 40% larger contact area vs conventional antibodies

    • Key interactions:

      • Heavy chain: Y102, W103 (hydrophobic core)

      • Light chain: E35 salt bridge

  • Functional correlate: Retains activity against BA.2.86 due to G485D accommodation in paratope .

How to optimize SMR8 dosing for in vivo tumor models?

  • PK/PD framework:

    • Establish target occupancy via PET imaging with 89Zr-labeled SMR8

    • Model exposure-response relationship:

      • EC50: 1.2 mg/kg (T cell infiltration)

      • EC90: 4.8 mg/kg (tumor regression)

    • Adjust for FcRn binding affinity (pH 6.0 retention >72hr) .

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