Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 211-221 |
| Journal | ACS Chemical Biology |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2016 |
| MoE publication type | A1 Journal article-refereed |
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Artificial avidin-based receptors for a panel of small molecules. / Lehtonen, Soili I.; Tullila, Antti; Agrawal, Nitin; Kukkurainen, Sampo; Kähkönen, Niklas; Koskinen, Masi; Nevanen, Tarja K.; Johnson, Mark S.; Airenne, Tomi T.; Kulomaa, Markku S.; Riihimäki, Tiina A.; Hytönen, Vesa P. (Corresponding Author).
In: ACS Chemical Biology, Vol. 11, No. 1, 2016, p. 211-221.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Artificial avidin-based receptors for a panel of small molecules
AU - Lehtonen, Soili I.
AU - Tullila, Antti
AU - Agrawal, Nitin
AU - Kukkurainen, Sampo
AU - Kähkönen, Niklas
AU - Koskinen, Masi
AU - Nevanen, Tarja K.
AU - Johnson, Mark S.
AU - Airenne, Tomi T.
AU - Kulomaa, Markku S.
AU - Riihimäki, Tiina A.
AU - Hytönen, Vesa P.
PY - 2016
Y1 - 2016
N2 - Proteins with high specificity, affinity, and stability are needed for biomolecular recognition in a plethora of applications. Antibodies are powerful affinity tools, but they may also suffer from limitations such as low stability and high production costs. Avidin and streptavidin provide a promising scaffold for protein engineering, and due to their ultratight binding to D-biotin they are widely used in various biotechnological and biomedical applications. In this study, we demonstrate that the avidin scaffold is suitable for use as a novel receptor for several biologically active small molecules: Artificial, chicken avidin-based proteins, antidins, were generated using a directed evolution method for progesterone, hydrocortisone, testosterone, cholic acid, ketoprofen, and folic acid, all with micromolar to nanomolar affinity and significantly reduced biotin-binding affinity. We also describe the crystal structure of an antidin, sbAvd-2(I117Y), a steroid-binding avidin, which proves that the avidin scaffold can tolerate significant modifications without losing its characteristic tetrameric beta-barrel structure, helping us to further design avidin-based small molecule receptors.
AB - Proteins with high specificity, affinity, and stability are needed for biomolecular recognition in a plethora of applications. Antibodies are powerful affinity tools, but they may also suffer from limitations such as low stability and high production costs. Avidin and streptavidin provide a promising scaffold for protein engineering, and due to their ultratight binding to D-biotin they are widely used in various biotechnological and biomedical applications. In this study, we demonstrate that the avidin scaffold is suitable for use as a novel receptor for several biologically active small molecules: Artificial, chicken avidin-based proteins, antidins, were generated using a directed evolution method for progesterone, hydrocortisone, testosterone, cholic acid, ketoprofen, and folic acid, all with micromolar to nanomolar affinity and significantly reduced biotin-binding affinity. We also describe the crystal structure of an antidin, sbAvd-2(I117Y), a steroid-binding avidin, which proves that the avidin scaffold can tolerate significant modifications without losing its characteristic tetrameric beta-barrel structure, helping us to further design avidin-based small molecule receptors.
U2 - 10.1021/acschembio.5b00906
DO - 10.1021/acschembio.5b00906
M3 - Article
VL - 11
SP - 211
EP - 221
JO - ACS Chemical Biology
JF - ACS Chemical Biology
SN - 1554-8929
IS - 1
ER -