Influence of acylation on the adsorption of GLP-2 to hydrophobic surfaces
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Influence of acylation on the adsorption of GLP-2 to hydrophobic surfaces. / Pinholt, Charlotte; Kapp, Sebastian J; Bukrinsky, Jens T; Hostrup, Susanne; Frokjaer, Sven; Norde, Willem; Jorgensen, Lene.
In: International Journal of Pharmaceutics, Vol. 440, No. 1, 2013, p. 63-71.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of acylation on the adsorption of GLP-2 to hydrophobic surfaces
AU - Pinholt, Charlotte
AU - Kapp, Sebastian J
AU - Bukrinsky, Jens T
AU - Hostrup, Susanne
AU - Frokjaer, Sven
AU - Norde, Willem
AU - Jorgensen, Lene
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2013
Y1 - 2013
N2 - Acylation of proteins with a fatty acid chain has proven useful for prolonging the plasma half-lives of proteins. In formulation of acylated protein drugs, knowledge about the effect of acylation with fatty acids on the adsorption behaviour of proteins at interfaces will be valuable. The aim of this work was to study the effect of acylation on the adsorption of GLP-2 from aqueous solution to a hydrophobic surface by comparing the adsorption of the 3766 Da GLP-2 with that of a GLP-2 variant acylated with a 16-carbon fatty acid chain through a ß-alanine linker. Adsorption of GLP-2 and acylated GLP-2 were studied with isothermal titration calorimetry, fixed-angle optical reflectometry and total internal reflection fluorescence. Furthermore, the effect of acylation of GLP-2 on the secondary structure was studied with Far-UV CD. Acylation was observed to have several effects on the adsorption of GLP-2. Acylation increased the amount of GLP-2 adsorbing per unit surface area and decreased the initial adsorption rate of GLP-2. Finally, acylation increased the strength of the adsorption, as judged by the lower fraction desorbing upon rinsing with buffer.
AB - Acylation of proteins with a fatty acid chain has proven useful for prolonging the plasma half-lives of proteins. In formulation of acylated protein drugs, knowledge about the effect of acylation with fatty acids on the adsorption behaviour of proteins at interfaces will be valuable. The aim of this work was to study the effect of acylation on the adsorption of GLP-2 from aqueous solution to a hydrophobic surface by comparing the adsorption of the 3766 Da GLP-2 with that of a GLP-2 variant acylated with a 16-carbon fatty acid chain through a ß-alanine linker. Adsorption of GLP-2 and acylated GLP-2 were studied with isothermal titration calorimetry, fixed-angle optical reflectometry and total internal reflection fluorescence. Furthermore, the effect of acylation of GLP-2 on the secondary structure was studied with Far-UV CD. Acylation was observed to have several effects on the adsorption of GLP-2. Acylation increased the amount of GLP-2 adsorbing per unit surface area and decreased the initial adsorption rate of GLP-2. Finally, acylation increased the strength of the adsorption, as judged by the lower fraction desorbing upon rinsing with buffer.
U2 - 10.1016/j.ijpharm.2012.01.040
DO - 10.1016/j.ijpharm.2012.01.040
M3 - Journal article
C2 - 22310460
VL - 440
SP - 63
EP - 71
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1
ER -
ID: 44287731