Biotechnology
Journal
DOI 10.1002/biot.201000380 Biotechnol. J. 2011, 6, 392–395
392 © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
eCG is a placental hormone secreted by the en-
dometrial cups of pregnant mares. eCG is a 60 kDa
glycoprotein hormone composed of two non-cova-
lently bound subunits. The average molecular
weights of the α and β subunits are 16.96 and
43.72 kDa,respectively.The total carbohydrate con-
tent of eCG is 45%, of which 10% correspond to sial-
ic acid. This contributes to the very low pI of 1.8 of
the hormone [1]. eCG can be detected in mare sera
between days 40 and 130 of gestation [2–4], with its
highest level of about 60–80 IU/mL in a bioassay in
the early state of pregnancy [5].
The classical procedure for the purification of
eCG is a multi-step precipitation process, followed
by chromatographic steps. The first step is a frac-
tionation with 0.5 M metaphosphoric acid at pH 3.0
and the discarding of the resulting precipitate. Af-
ter the adjustment of the pH of the supernatant to
4.5, followed by the addition of one volume of cold
(-20°C) ethanol, the solution is allowed to precipi-
tate for 2 h at 4°C. Subsequently, after discarding
the precipitate again, the ethanol fraction in the su-
pernatant is raised up to 75% v/v.The resulting pre-
cipitate is collected after 20 h at 4°C, dialyzed or di-
afiltrated, and lyophilized [6]. The final cleaning
consists of two fixed-bed chromatographic steps,
including ion exchange and gel filtration.
In contrast to this complex procedure, we devel-
oped two simplified processes for the purification
of eCG based on the application of magnetic mi-
croadsorbents. The first process comprises only
two precipitation steps, followed by an ultra-/di-
afiltration step and a final purification step using
magnetic anion exchange (AIX) microadsorbents
synthesized by a reaction of carboxylated magnet-
ic polyvinyl beads (M-PVA) with N,N-diethyl-am-
monium as functional groups. Due to of the high
salt and protein contents, direct application of the
magnetic AIX adsorbents in untreated serum is im-
possible. Nevertheless, the process described is
less time-consuming and requires only 1/3 of sol-
Short Communication
Gonadotropin purification from horse serum applying
magnetic beads
Christine Müller
1
, Andrea Preußer-Kunze
2
, Kerstin Wagner
3
and Matthias Franzreb
1
1
Karlsruhe Institute of Technology, Institute of Functional Interfaces, Germany
2
fzmb GmbH Institute for Medical Technology and Biotechnology, Germany
3
INNOVENT e.V., Biomaterials Department, Germany
The glycoprotein hormone equine chorionic gonadotropin (eCG) is a commercial product used in
animal breeding as well as in veterinary medicine. The current state of the art for the purification
of eCG from serum is pH fractionation with metaphosphoric acid, two ethanol precipitation steps
as well as dialysis followed by fixed-bed chromatography. Two simplified processes, including the
use of magnetic microsorbents for the purification of eCG have been developed. The processes
reduce or even omit the use of organic solvents and the required solid–liquid separation steps,
thus making them potential candidates for a first commercial application of magnetic beads in
bioprocessing.
Keywords: Equine chorionic gonadotropin · Magnetic adsorbents · Purification · Serum
Correspondence: Professor Matthias Franzreb, Karlsruhe Institute of
Technology, Institute of Functional Interfaces, Hermann-von-Helmholtz-
Platz, 176344 Eggenstein Leopoldshafen, Germany
Fax: +49-7247-823478
E-mail: matthias.franzreb@kit.edu
Abbreviations: AIX, anion exchange; eCG, equine chorionic gonadotropin;
HGMF, high-gradient magnetic fishing
Received 29 October 2010
Revised 7 December 2010
Accepted 9 December 2010