Structural and Hydrodynamic Analysis of a Novel Drug Delivery Vector: ELP[V5G3A2-150]
| Autor: | Edwin A. Lewis, Drazen Raucher, Daniel F. Lyons, Wolfgang Kramer, Vu H. Le, Gene L. Bidwell, John J. Correia |
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| Rok vydání: | 2013 |
| Předmět: |
Drug Carriers
Chemistry Molecular Sequence Data Temperature Biophysics Proteins Conjugated system Protein Structure Secondary Random coil Elastin Hydrophobic effect Solubility Covalent bond Drug delivery Organic chemistry Amino Acid Sequence Proteins and Nucleic Acids Drug carrier Hydrophobic and Hydrophilic Interactions Oligopeptides Conjugate |
| Zdroj: | Biophysical Journal. 104:2009-2021 |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2013.03.040 |
| Popis: | The therapeutic potential of elastin-like polypeptide (ELP) conjugated to therapeutic compounds is currently being investigated as an approach to target drugs to solid tumors. ELPs are hydrophobic polymers that are soluble at low temperatures and cooperatively aggregate above a transition temperature (TT), allowing for thermal targeting of covalently attached drugs. They have been shown to cooperatively transition from a disordered structure to a repeating type II β-turn structure, forming a β-spiral above the TT. Here we present biophysical measurements of the structural, thermodynamic, and hydrodynamic properties of a specific ELP being investigated for drug delivery, ELP[V5G3A2-150]. We examine the biophysical properties below and above the TT to understand and predict the therapeutic potential of ELP-drug conjugates. We observed that below the TT, ELP[V5G3A2-150] is soluble, with an extended conformation consisting of both random coil and heterogeneous β structures. Sedimentation velocity experiments indicate that ELP[V5G3A2-150] undergoes weak self-association with increasing temperature, and above the TT the hydrophobic effect drives aggregation entropically. These experiments also reveal a previously unreported temperature-dependent critical concentration (Cc) that resembles a solubility constant. Labeling ELP[V5G3A2-150] with fluorescein lowers the TT by 3.5°C at 20 μM, whereas ELP[V5G3A2-150] dissolution in physiological media (fetal bovine serum) increases the TT by ∼2.2°C. |
| Databáze: | OpenAIRE |
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