Rapid isolation of peptidic inhibitors of the solute carrier family transporters OATP1B1 and OATP1B3 by cell-based phage display selections

OATP1B1 and OATP1B3 (1B3) are members of organic anion-transporting polypeptides (OATPs), a family of sodium-independent organic anion membrane transporters that contribute to transport of various drugs. To identify peptide inhibitors of OATP1B1, we developed a direct selection system on live cells...

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Veröffentlicht in:Biochemical and biophysical research communications 2016-04, Vol.473 (2), p.370-376
Hauptverfasser: Arita, Yuko, Allen, Samantha, Chen, Gang, Zhang, Wei, Wang, Ying, Owen, Albert J., Dentinger, Patrick, Sidhu, Sachdev S.
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container_issue 2
container_start_page 370
container_title Biochemical and biophysical research communications
container_volume 473
creator Arita, Yuko
Allen, Samantha
Chen, Gang
Zhang, Wei
Wang, Ying
Owen, Albert J.
Dentinger, Patrick
Sidhu, Sachdev S.
description OATP1B1 and OATP1B3 (1B3) are members of organic anion-transporting polypeptides (OATPs), a family of sodium-independent organic anion membrane transporters that contribute to transport of various drugs. To identify peptide inhibitors of OATP1B1, we developed a direct selection system on live cells using phage-displayed peptide libraries. Selections against OATP1B1 overexpressed cell-lines yielded three unique peptides able to inhibit the transport function of OATP1B1 and 1B3. Affinity maturation of one peptide led to identification of two peptides that demonstrated improved inhibition efficacy on drug uptake mediated by OATP1B1 and 1B3. We anticipate that these peptides will assist the identification of novel substrates for OATP1B1 and 1B3. Moreover, our selection system is a practical method for generating inhibitors of other membrane transporters. [Display omitted] •Identification of peptide inhibitors for OATP1B1 and OATP1B3.•Construction of phage-displayed peptide library with high diversity.•Development of phage-display selections for membrane transports using live cell.
doi_str_mv 10.1016/j.bbrc.2016.01.050
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ispartof Biochemical and biophysical research communications, 2016-04, Vol.473 (2), p.370-376
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language eng
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source MEDLINE; Elsevier ScienceDirect Journals
subjects 5′CF
6′CF
Amino Acid Sequence
ASP
bacteriophages
Biological Transport - drug effects
CDC-NBD
Drug Discovery
drugs
fMTX
HEK293 Cells
Humans
Molecular Sequence Data
NTCP
OAT1
OAT3
OATP1B1
OATP1B3
OCT1
OCT2
Organic Anion Transporters - antagonists & inhibitors
Organic Anion Transporters - metabolism
Organic Anion Transporters, Sodium-Independent - antagonists & inhibitors
Organic Anion Transporters, Sodium-Independent - metabolism
Organic anion-transporting polypeptides
Peptide inhibitor
peptide libraries
Peptide Library
Peptides - chemistry
Peptides - pharmacology
Phage-display
polypeptides
Solute Carrier Organic Anion Transporter Family Member 1b1
Solute Carrier Organic Anion Transporter Family Member 1B3
solutes
transporters
title Rapid isolation of peptidic inhibitors of the solute carrier family transporters OATP1B1 and OATP1B3 by cell-based phage display selections
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