Abstract
Thymosin Beta-4 (TB-4) is a 43-amino-acid, 4.9 kDa actin-sequestering peptide expressed ubiquitously in mammalian tissues. Its primary physiological role is regulation of the G-actin/F-actin equilibrium through 1:1 binding to monomeric actin. The N-terminal fragment Ac-LKKTETQ (TB-500) retains most of the actin-binding activity at lower molecular weight.
Molecular Background
Key characteristics of TB-4 and TB-500:
- TB-4 is encoded by the highly conserved X-chromosomal gene TMSB4X
- Central actin-binding motif: LKKTETQ (residues 17-23)
- High affinity G-actin binding (Kd ≈ 0.4 µM)
- Intrinsically disordered structure, adopts β-hairpin upon actin binding
- Both forms stable in plasma (t½ > 2 hours)
Research Applications
TB-500 has been investigated in laboratory settings for:
- Cell Migration Studies: Actin-mediated motility research
- Wound Healing: Dermal and corneal repair mechanisms
- Cardiac Research: Myocardial regeneration studies
- Anti-inflammatory Research: Inflammatory marker modulation
- Hair Biology: Follicle cycling and growth studies
Proposed Mechanisms
- Actin Sequestration: Lowering F-actin stress fibers to facilitate migration
- VEGF Induction: Angiogenesis promotion
- MMP Activation: Matrix remodeling processes
- NF-κB Inhibition: Anti-inflammatory effects
- PIN1 Binding: Isomerization of phosphorylated substrates
Preclinical Research Summary
Research models have included:
- Dermal wound closure models
- Corneal injury and regeneration
- Myocardial infarction models
- Spinal cord contusion studies
- Hair regrowth investigations
Technical Specifications
- Molecular Formula: C212H350N56O78S
- Molecular Weight: 4963.44 g/mol
- Purity: ≥99% (HPLC verified)
- Storage: Store lyophilized at -20°C
Current Research Status
TB-4 has progressed to early-phase human trials in specific applications such as wound healing and dry eye. The combination of mechanistic understanding and preclinical efficacy positions TB-500 as one of the more validated peptides in regenerative research.