Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells

J. Matuliene; G. Zvinys; V. Petrauskas; A. Kvietkauskaite; A. Zaksauskas; K. Shubin; A. Zubriene; L. Baranauskiene; L. Kacenauskaite; S. Kopanchuk; S. Veiksina; V. Paketuryte-Latve; J. Smirnoviene; V. Juozapaitiene; A. Mickeviciute; V. Michailoviene; J. Jachno; D. Stravinskiene; A. Sliziene; A. Petrosiute; H.M. Becker; J. Kazokaite-Adomaitiene; A. Yaromina; E. Capkauskaite; A. Rinken; V. Dudutiene; L.J. Dubois; D. Matulis

doi:10.1038/s41598-022-22436-1

Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells

J. Matuliene, G. Zvinys, V. Petrauskas, A. Kvietkauskaite, A. Zaksauskas, K. Shubin, A. Zubriene, L. Baranauskiene, L. Kacenauskaite, S. Kopanchuk, S. Veiksina, V. Paketuryte-Latve, J. Smirnoviene, V. Juozapaitiene, A. Mickeviciute, V. Michailoviene, J. Jachno, D. Stravinskiene, A. Sliziene, A. PetrosiuteH.M. Becker, J. Kazokaite-Adomaitiene, A. Yaromina, E. Capkauskaite, A. Rinken, V. Dudutiene, L.J. Dubois, D. Matulis^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Numerous human cancers, especially hypoxic solid tumors, express carbonic anhydrase IX (CAIX), a transmembrane protein with its catalytic domain located in the extracellular space. CAIX acidifies the tumor microenvironment, promotes metastases and invasiveness, and is therefore considered a promising anticancer target. We have designed a series of high affinity and high selectivity fluorescein-labeled compounds targeting CAIX to visualize and quantify CAIX expression in cancer cells. The competitive binding model enabled the determination of common CA inhibitors' dissociation constants for CAIX expressed in exponentially growing cancer cells. All tested sulfonamide compounds bound the proliferating cells with similar affinity as to recombinantly purified CAIX. The probes are applicable for the design of selective drug-like compounds for CAIX and the competition strategy could be applied to other drug targets.

Original language	English
Article number	17644
Number of pages	25
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-22436-1
Publication status	Published - 21 Oct 2022

Keywords

FLUORINATED BENZENESULFONAMIDES
INTRINSIC THERMODYNAMICS
SELECTIVE INHIBITORS
LIGAND-BINDING
X-RAY
SULFONAMIDE
PROTEIN
MARKER
ASSAY
XII

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Matuliene, J., Zvinys, G., Petrauskas, V., Kvietkauskaite, A., Zaksauskas, A., Shubin, K., Zubriene, A., Baranauskiene, L., Kacenauskaite, L., Kopanchuk, S., Veiksina, S., Paketuryte-Latve, V., Smirnoviene, J., Juozapaitiene, V., Mickeviciute, A., Michailoviene, V., Jachno, J., Stravinskiene, D., Sliziene, A., ... Matulis, D. (2022). Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells. Scientific Reports, 12(1), Article 17644. https://doi.org/10.1038/s41598-022-22436-1

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title = "Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells",

abstract = "Numerous human cancers, especially hypoxic solid tumors, express carbonic anhydrase IX (CAIX), a transmembrane protein with its catalytic domain located in the extracellular space. CAIX acidifies the tumor microenvironment, promotes metastases and invasiveness, and is therefore considered a promising anticancer target. We have designed a series of high affinity and high selectivity fluorescein-labeled compounds targeting CAIX to visualize and quantify CAIX expression in cancer cells. The competitive binding model enabled the determination of common CA inhibitors' dissociation constants for CAIX expressed in exponentially growing cancer cells. All tested sulfonamide compounds bound the proliferating cells with similar affinity as to recombinantly purified CAIX. The probes are applicable for the design of selective drug-like compounds for CAIX and the competition strategy could be applied to other drug targets.",

keywords = "FLUORINATED BENZENESULFONAMIDES, INTRINSIC THERMODYNAMICS, SELECTIVE INHIBITORS, LIGAND-BINDING, X-RAY, SULFONAMIDE, PROTEIN, MARKER, ASSAY, XII",

author = "J. Matuliene and G. Zvinys and V. Petrauskas and A. Kvietkauskaite and A. Zaksauskas and K. Shubin and A. Zubriene and L. Baranauskiene and L. Kacenauskaite and S. Kopanchuk and S. Veiksina and V. Paketuryte-Latve and J. Smirnoviene and V. Juozapaitiene and A. Mickeviciute and V. Michailoviene and J. Jachno and D. Stravinskiene and A. Sliziene and A. Petrosiute and H.M. Becker and J. Kazokaite-Adomaitiene and A. Yaromina and E. Capkauskaite and A. Rinken and V. Dudutiene and L.J. Dubois and D. Matulis",

note = "Funding Information: This work was supported by the grant S-SEN-20-10 to JM from the Research Council of Lithuania and Estonian Research Council grant PSG230. HMB thanks Antje Beyer for technical assistance. AP thanks Asta Lu{\v c}iūnaitė and Virginija Bukelskienė for assistance. Funding Information: This work was supported by the grant S-SEN-20-10 to JM from the Research Council of Lithuania and Estonian Research Council grant PSG230. HMB thanks Antje Beyer for technical assistance. AP thanks Asta Lu{\v c}iūnaitė and Virginija Bukelskienė for assistance. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = oct,

day = "21",

doi = "10.1038/s41598-022-22436-1",

language = "English",

volume = "12",

journal = "Scientific Reports",

issn = "2045-2322",

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Matuliene, J, Zvinys, G, Petrauskas, V, Kvietkauskaite, A, Zaksauskas, A, Shubin, K, Zubriene, A, Baranauskiene, L, Kacenauskaite, L, Kopanchuk, S, Veiksina, S, Paketuryte-Latve, V, Smirnoviene, J, Juozapaitiene, V, Mickeviciute, A, Michailoviene, V, Jachno, J, Stravinskiene, D, Sliziene, A, Petrosiute, A, Becker, HM, Kazokaite-Adomaitiene, J, Yaromina, A, Capkauskaite, E, Rinken, A, Dudutiene, V, Dubois, LJ & Matulis, D 2022, 'Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells', Scientific Reports, vol. 12, no. 1, 17644. https://doi.org/10.1038/s41598-022-22436-1

TY - JOUR

T1 - Picomolar fluorescent probes for compound affinity determination to carbonic anhydrase IX expressed in live cancer cells

AU - Matuliene, J.

AU - Zvinys, G.

AU - Petrauskas, V.

AU - Kvietkauskaite, A.

AU - Zaksauskas, A.

AU - Shubin, K.

AU - Zubriene, A.

AU - Baranauskiene, L.

AU - Kacenauskaite, L.

AU - Kopanchuk, S.

AU - Veiksina, S.

AU - Paketuryte-Latve, V.

AU - Smirnoviene, J.

AU - Juozapaitiene, V.

AU - Mickeviciute, A.

AU - Michailoviene, V.

AU - Jachno, J.

AU - Stravinskiene, D.

AU - Sliziene, A.

AU - Petrosiute, A.

AU - Becker, H.M.

AU - Kazokaite-Adomaitiene, J.

AU - Yaromina, A.

AU - Capkauskaite, E.

AU - Rinken, A.

AU - Dudutiene, V.

AU - Dubois, L.J.

AU - Matulis, D.

N1 - Funding Information: This work was supported by the grant S-SEN-20-10 to JM from the Research Council of Lithuania and Estonian Research Council grant PSG230. HMB thanks Antje Beyer for technical assistance. AP thanks Asta Lučiūnaitė and Virginija Bukelskienė for assistance. Funding Information: This work was supported by the grant S-SEN-20-10 to JM from the Research Council of Lithuania and Estonian Research Council grant PSG230. HMB thanks Antje Beyer for technical assistance. AP thanks Asta Lučiūnaitė and Virginija Bukelskienė for assistance. Publisher Copyright: © 2022, The Author(s).

PY - 2022/10/21

Y1 - 2022/10/21

N2 - Numerous human cancers, especially hypoxic solid tumors, express carbonic anhydrase IX (CAIX), a transmembrane protein with its catalytic domain located in the extracellular space. CAIX acidifies the tumor microenvironment, promotes metastases and invasiveness, and is therefore considered a promising anticancer target. We have designed a series of high affinity and high selectivity fluorescein-labeled compounds targeting CAIX to visualize and quantify CAIX expression in cancer cells. The competitive binding model enabled the determination of common CA inhibitors' dissociation constants for CAIX expressed in exponentially growing cancer cells. All tested sulfonamide compounds bound the proliferating cells with similar affinity as to recombinantly purified CAIX. The probes are applicable for the design of selective drug-like compounds for CAIX and the competition strategy could be applied to other drug targets.

AB - Numerous human cancers, especially hypoxic solid tumors, express carbonic anhydrase IX (CAIX), a transmembrane protein with its catalytic domain located in the extracellular space. CAIX acidifies the tumor microenvironment, promotes metastases and invasiveness, and is therefore considered a promising anticancer target. We have designed a series of high affinity and high selectivity fluorescein-labeled compounds targeting CAIX to visualize and quantify CAIX expression in cancer cells. The competitive binding model enabled the determination of common CA inhibitors' dissociation constants for CAIX expressed in exponentially growing cancer cells. All tested sulfonamide compounds bound the proliferating cells with similar affinity as to recombinantly purified CAIX. The probes are applicable for the design of selective drug-like compounds for CAIX and the competition strategy could be applied to other drug targets.

KW - FLUORINATED BENZENESULFONAMIDES

KW - INTRINSIC THERMODYNAMICS

KW - SELECTIVE INHIBITORS

KW - LIGAND-BINDING

KW - X-RAY

KW - SULFONAMIDE

KW - PROTEIN

KW - MARKER

KW - ASSAY

KW - XII

U2 - 10.1038/s41598-022-22436-1

DO - 10.1038/s41598-022-22436-1

M3 - Article

C2 - 36271018

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 17644

ER -