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  • Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity.

Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity.

Journal of liposome research (2014-03-07)
Melvin E Klegerman, Yuejiao Zou, Eva Golunski, Tao Peng, Shao-Ling Huang, David D McPherson
ABSTRACT

Thermodynamic analysis of ligand-target binding has been a useful tool for dissecting the nature of the binding mechanism and, therefore, potentially can provide valuable information regarding the utility of targeted formulations. Based on a consistent coupling of antibody-antigen binding and gel-liquid crystal transition energetics observed for antibody-phosphatidylethanolamine (Ab-PE) conjugates, we hypothesized that the thermodynamic parameters and the affinity for antigen of the Ab-PE conjugates could be effectively predicted once the corresponding information for the unconjugated antibody is determined. This hypothesis has now been tested in nine different antibody-targeted echogenic liposome (ELIP) preparations, where antibody is conjugated to dipalmitoylphosphatidylethanolamine (DPPE) head groups through a thioether linkage. Predictions were satisfactory (affinity not significantly different from the population of values found) in five cases (55.6%), but the affinity of the unconjugated antibody was not significantly different from the population of values found in six cases (66.7%), indicating that the affinities of the conjugated antibody tended not to deviate appreciably from those of the free antibody. While knowledge of the affinities of free antibodies may be sufficient to judge their suitability as targeting agents, thermodynamic analysis may still provide valuable information regarding their usefulness for specific applications.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human CEA ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Argon, ≥99.998%
Sigma-Aldrich
Argon-40Ar, 99.95 atom %
Sigma-Aldrich
3-(2-Pyridyldithio)propionic acid N-hydroxysuccinimide ester, ≥95%, powder