Abstract:
: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 β-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.
journal_name
Int J Pharmjournal_title
International journal of pharmaceuticsauthors
Pinholt C,Kapp SJ,Bukrinsky JT,Hostrup S,Frokjaer S,Norde W,Jorgensen Ldoi
10.1016/j.ijpharm.2012.01.040subject
Has Abstractpub_date
2013-01-02 00:00:00pages
63-71issue
1eissn
0378-5173issn
1873-3476pii
S0378-5173(12)00094-4journal_volume
440pub_type
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