Artificial avidin-based receptors for a panel of small molecules

Soili I. Lehtonen, Antti Tullila, Nitin Agrawal, Sampo Kukkurainen, Niklas Kähkönen, Masi Koskinen, Tarja K. Nevanen, Mark S. Johnson, Tomi T. Airenne, Markku S. Kulomaa, Tiina A. Riihimäki, Vesa P. Hytönen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)211-221
JournalACS Chemical Biology
Volume11
Issue number1
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Fingerprint

Avidin
Molecules
Scaffolds
Biotin
Cholic Acid
Protein Engineering
Ketoprofen
Proteins
Antibody Affinity
Streptavidin
Folic Acid
Progesterone
Hydrocortisone
Testosterone
Chickens
Crystal structure
Steroids
Costs and Cost Analysis
Antibodies
Costs

Cite this

Lehtonen, S. I., Tullila, A., Agrawal, N., Kukkurainen, S., Kähkönen, N., Koskinen, M., ... Hytönen, V. P. (2016). Artificial avidin-based receptors for a panel of small molecules. ACS Chemical Biology, 11(1), 211-221. https://doi.org/10.1021/acschembio.5b00906
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. / Artificial avidin-based receptors for a panel of small molecules. In: ACS Chemical Biology. 2016 ; Vol. 11, No. 1. pp. 211-221.
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Lehtonen, SI, Tullila, A, Agrawal, N, Kukkurainen, S, Kähkönen, N, Koskinen, M, Nevanen, TK, Johnson, MS, Airenne, TT, Kulomaa, MS, Riihimäki, TA & Hytönen, VP 2016, 'Artificial avidin-based receptors for a panel of small molecules', ACS Chemical Biology, vol. 11, no. 1, pp. 211-221. https://doi.org/10.1021/acschembio.5b00906

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 journalArticleScientificpeer-review

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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.

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DO - 10.1021/acschembio.5b00906

M3 - Article

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EP - 221

JO - ACS Chemical Biology

JF - ACS Chemical Biology

SN - 1554-8929

IS - 1

ER -

Lehtonen SI, Tullila A, Agrawal N, Kukkurainen S, Kähkönen N, Koskinen M et al. Artificial avidin-based receptors for a panel of small molecules. ACS Chemical Biology. 2016;11(1):211-221. https://doi.org/10.1021/acschembio.5b00906