Biophysical Analysis of a Novel Drug Delivery Vector: ELP[V5G3A2-150]
| Autor: | Vu H. Le, Ed Lewis, Drazen Raucher, Gene L. Bidwell, Daniel F. Lyons, Wolfgang Kramer, John J. Correia |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0303 health sciences
Tropoelastin biology Chemistry Transition temperature Quantitative Biology::Molecular Networks Biophysics Blood proteins Quantitative Biology::Cell Behavior 03 medical and health sciences Crystallography 0302 clinical medicine In vivo Drug delivery biology.protein Solubility Macromolecular crowding 030217 neurology & neurosurgery 030304 developmental biology Conjugate |
| Zdroj: | Biophysical Journal. (2):552a-553a |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2012.11.3065 |
| Popis: | Elastin-like Polypeptides (ELPs) are genetically engineered biopolymers that are derived from the endogenous protein Tropoelastin. ELPs are structurally disordered and soluble at low temperatures but transition to a β-spiral and aggregate at a Transition Temperature (TT). This aggregation is being explored as a novel drug delivery vector by thermally targeting systemically delivered ELP-drug conjugates. We are investigating the biophysical properties of ELP[V5G3A2-150] as a means of understanding and predicting the behavior in vivo. We have investigated the hydrodynamic, structural and thermodynamic properties of ELP[V5G3A2-150] through the use of CD, turbidity, DLS, DSC and SV. DLS and SV analyses suggest that ELP[V5G3A2-150] experiences small amounts of weak association below the TT that increase with temperature. CD analyses further indicate that below the TT ELP[V5G3A2-150] consists of both disordered (≈75%) and β-conformation (≈25%) and as the temperature and concentration is increased the % β-conformation increases. The temperature & concentration dependence of β-conformation suggests that the weak association can be attributed to heterogeneous β-sheets. SV revealed that above the TT ELP[V5G3A2-150] exhibits a temperature dependent critical concentration (CC). This CC is consistent with the TT and suggests that the TT may be described as a solubility constant.Assembly in serum raises the TT by ≈ 2.5°C. This is opposite to the expected effect of macromolecular crowding and suggests that certain serum proteins may be associating with ELP[V5G3A2-150]. Investigation of this effect through SV was greatly complicated by the presence of the Johnston-Ogston (J-O) effect. Further investigation suggested additional complexity in systems exhibiting the J-O effect than previously reported. Two of the additional complexities already determined are cross-term hydrodynamic non-ideality and high-concentration convection. Additional research into the effects of attaching CPPs to ELP[V5G3A2-150] will be presented. Work supported by NSF ARRA 0959211 grant. |
| Databáze: | OpenAIRE |
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