Influence of acylation on the adsorption of GLP-2 to hydrophobic surfaces

被引：14

作者：

Pinholt, Charlotte ^{[1
]}

Kapp, Sebastian J. ^{[1
]}

Bukrinsky, Jens T. ^{[2
]}

Hostrup, Susanne ^{[3
]}

Frokjaer, Sven ^{[1
]}

Norde, Willem ^{[4
,5
,6
]}

Jorgensen, Lene ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharmaceut & Analyt Chem, DK-2100 Copenhagen, Denmark

[2] Novozymes Biopharma DK AS, DK-2800 Bagsvaerd, Denmark

[3] Novo Nordisk AS, DK-2760 Malov, Denmark

[4] Wageningen Univ, Lab Phys Chem & Colloid Sci, NL-6700 AP Wageningen, Netherlands

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Biomed Engn, Groningen, Netherlands

[6] Univ Groningen, NL-9700 AB Groningen, Netherlands

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2013年 / 440卷 / 01期

关键词：

Acylation; Protein adsorption; GLP-2; ITC; Reflectometry; TIRF; GLUCAGON-LIKE PEPTIDE-2; PROTEIN ADSORPTION; REVERSIBLE LIPIDIZATION; INSULIN; ALBUMIN; DESMOPRESSIN; FLUORESCENCE; CONJUGATION; KINETICS; DELIVERY;

D O I：

10.1016/j.ijpharm.2012.01.040

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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 beta-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. (C) 2012 Elsevier B.V. All rights reserved.

引用

页码：63 / 71

页数：9

共 46 条

[1]

[Anonymous], COMMUNICATION

[2]

[Anonymous], PROTEIN ADSORPTION

[3]

[Anonymous], PROTEOMICS PROTOCOLS

[4] ADSORPTION OF INSULIN ON METAL-SURFACES IN RELATION TO ASSOCIATION BEHAVIOR [J].

ARNEBRANT, T ;

NYLANDER, T .

JOURNAL OF COLLOID AND INTERFACE SCIENCE, 1988, 122 (02) :557-566

[5] Conjugation of a magainin analogue with lipophilic acids controls hydrophobicity, solution assembly, and cell selectivity [J].

Avrahami, D ;

Shai, Y .

BIOCHEMISTRY, 2002, 41 (07) :2254-2263

[6] Adsorption kinetics, conformation, and mobility of the growth hormone and lysozyme on solid surfaces, studied with TIRF [J].

Buijs, J ;

Hlady, V .

JOURNAL OF COLLOID AND INTERFACE SCIENCE, 1997, 190 (01) :171-181

[7] FLUORESCENCE AND LOCATION OF TRYPTOPHAN RESIDUES IN PROTEIN MOLECULES [J].

BURSTEIN, EA ;

VEDENKINA, NS ;

IVKOVA, MN .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1973, 18 (04) :263-279

[8] KINETICS OF POLYMER ADSORPTION IN STAGNATION POINT FLOW [J].

DIJT, JC ;

STUART, MAC ;

HOFMAN, JE ;

FLEER, GJ .

COLLOIDS AND SURFACES, 1990, 51 :141-158

[9] In vivo and in vitro degradation of glucagon-like peptide-2 in humans [J].

Hartmann, B ;

Harr, MB ;

Jeppesen, PB ;

Wojdemann, M ;

Deacon, CF ;

Mortensen, PB ;

Holst, JJ .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (08) :2884-2888

[10] The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin [J].

Havelund, S ;

Plum, A ;

Ribel, U ;

Jonassen, I ;

Volund, A ;

Markussen, J ;

Kurtzhals, P .

PHARMACEUTICAL RESEARCH, 2004, 21 (08) :1498-1504

← 1 2 3 4 5 →