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Presentation Abstract
Session Title:
Platform: Protein Assemblies, Aggregates, & Chaperones
Location:
Room 113C
Presentation Number:
2838-Plat
Presentation Time:
2/6/2013 1:00:00 PM
Abstract Title:
BIOPHYSICAL ANALYSIS OF A NOVEL DRUG DELIVERY VECTOR: ELP[V5G3A2-150]
Author Block:
Daniel Lyons
1
, Vu Le
2
, Gene L. Bidwell
1
, Wolfgang Kramer
3
, Ed Lewis
2
, Drazen Raucher
1
, John J. Correia
1
.
1
University of Mississippi Medical Center, Jackson, MS, USA,
2
Mississippi State University, Starkville, MS, USA,
3
Millsaps College, Jackson, MS, USA.
Abstract Body:
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 (T
T
). 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[V
5
G
3
A
2
-150] as a means of understanding and predicting the behavior
in vivo
. We have investigated the hydrodynamic, structural and thermodynamic properties of ELP[V
5
G
3
A
2
-150] through the use of CD, turbidity, DLS, DSC and SV. DLS and SV analyses suggest that ELP[V
5
G
3
A
2
-150] experiences small amounts of weak association below the T
T
that increase with temperature. CD analyses further indicate that below the T
T
ELP[V
5
G
3
A
2
-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 T
T
ELP[V
5
G
3
A
2
-150] exhibits a temperature dependent critical concentration (C
C
). This C
C
is consistent with the T
T
and suggests that the T
T
may be described as a solubility constant.
Assembly in serum raises the T
T
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[V
5
G
3
A
2
-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[V
5
G
3
A
2
-150] will be presented. Work supported by NSF ARRA 0959211 grant.
Commercial Relationship:
D. Lyons:
None.
V. Le:
None.
G.L. Bidwell:
None.
W. Kramer:
None.
E. Lewis:
None.
D. Raucher:
None.
J.J. Correia:
None.
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