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 |
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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 |
format | Article |
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[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.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2016.01.050</identifier><identifier>PMID: 26792727</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>5â²CF ; 6â²CF ; 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</subject><ispartof>Biochemical and biophysical research communications, 2016-04, Vol.473 (2), p.370-376</ispartof><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-a4945c69cf2a95bdccd601819d2955cfeba4a27de1e200157611ff11e6c1271d3</citedby><cites>FETCH-LOGICAL-c380t-a4945c69cf2a95bdccd601819d2955cfeba4a27de1e200157611ff11e6c1271d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X1630050X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26792727$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arita, Yuko</creatorcontrib><creatorcontrib>Allen, Samantha</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Owen, Albert J.</creatorcontrib><creatorcontrib>Dentinger, Patrick</creatorcontrib><creatorcontrib>Sidhu, Sachdev S.</creatorcontrib><title>Rapid isolation of peptidic inhibitors of the solute carrier family transporters OATP1B1 and OATP1B3 by cell-based phage display selections</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><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.</description><subject>5â²CF</subject><subject>6â²CF</subject><subject>Amino Acid Sequence</subject><subject>ASP</subject><subject>bacteriophages</subject><subject>Biological Transport - drug effects</subject><subject>CDC-NBD</subject><subject>Drug Discovery</subject><subject>drugs</subject><subject>fMTX</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Molecular Sequence Data</subject><subject>NTCP</subject><subject>OAT1</subject><subject>OAT3</subject><subject>OATP1B1</subject><subject>OATP1B3</subject><subject>OCT1</subject><subject>OCT2</subject><subject>Organic Anion Transporters - antagonists & inhibitors</subject><subject>Organic Anion Transporters - metabolism</subject><subject>Organic Anion Transporters, Sodium-Independent - antagonists & inhibitors</subject><subject>Organic Anion Transporters, Sodium-Independent - metabolism</subject><subject>Organic anion-transporting polypeptides</subject><subject>Peptide inhibitor</subject><subject>peptide libraries</subject><subject>Peptide Library</subject><subject>Peptides - chemistry</subject><subject>Peptides - pharmacology</subject><subject>Phage-display</subject><subject>polypeptides</subject><subject>Solute Carrier Organic Anion Transporter Family Member 1b1</subject><subject>Solute Carrier Organic Anion Transporter Family Member 1B3</subject><subject>solutes</subject><subject>transporters</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2O0zAUhS0EYsrAC7AAL9kk3OvGTi2xGUb8SSMNghmJneXYN1NXaRzsFKnPwEvjqIUlK19Z3z0-Poexlwg1Aqq3u7rrkqtFmWvAGiQ8YisEDZVAaB6zFQCoSmj8ccGe5bwDQGyUfsouhGq1aEW7Yr-_2Sl4HnIc7BziyGPPJ5rm4IPjYdyGLswx5eV63hIv2GEm7mxKgRLv7T4MRz4nO-YpppkKeXt19xXfI7ejP89r3h25o2GoOpvJ82lrH4j7kKfBHnmmgdzydH7OnvR2yPTifF6y-48f7q4_Vze3n75cX91Ubr2BubKNbqRT2vXCatl557wC3KD2QkvpeupsY0XrCUmUL8tWIfY9IimHokW_vmRvTrpTij8PlGezD3nxZ0eKh2yw3QiBSgooqDihLsWcE_VmSmFv09EgmKUEszNLCWYpwQCaUkJZenXWP3R78v9W_qZegNcnoLfR2IcUsrn_vigUu1pCKwvx7kRQyeFXidpkF2h05EMqaRkfw_8c_AHW-aJk</recordid><startdate>20160429</startdate><enddate>20160429</enddate><creator>Arita, Yuko</creator><creator>Allen, Samantha</creator><creator>Chen, Gang</creator><creator>Zhang, Wei</creator><creator>Wang, Ying</creator><creator>Owen, Albert J.</creator><creator>Dentinger, Patrick</creator><creator>Sidhu, Sachdev S.</creator><general>Elsevier Inc</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20160429</creationdate><title>Rapid isolation of peptidic inhibitors of the solute carrier family transporters OATP1B1 and OATP1B3 by cell-based phage display selections</title><author>Arita, Yuko ; Allen, Samantha ; Chen, Gang ; Zhang, Wei ; Wang, Ying ; Owen, Albert J. ; Dentinger, Patrick ; Sidhu, Sachdev S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-a4945c69cf2a95bdccd601819d2955cfeba4a27de1e200157611ff11e6c1271d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>5â²CF</topic><topic>6â²CF</topic><topic>Amino Acid Sequence</topic><topic>ASP</topic><topic>bacteriophages</topic><topic>Biological Transport - drug effects</topic><topic>CDC-NBD</topic><topic>Drug Discovery</topic><topic>drugs</topic><topic>fMTX</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Molecular Sequence Data</topic><topic>NTCP</topic><topic>OAT1</topic><topic>OAT3</topic><topic>OATP1B1</topic><topic>OATP1B3</topic><topic>OCT1</topic><topic>OCT2</topic><topic>Organic Anion Transporters - antagonists & inhibitors</topic><topic>Organic Anion Transporters - metabolism</topic><topic>Organic Anion Transporters, Sodium-Independent - antagonists & inhibitors</topic><topic>Organic Anion Transporters, Sodium-Independent - metabolism</topic><topic>Organic anion-transporting polypeptides</topic><topic>Peptide inhibitor</topic><topic>peptide libraries</topic><topic>Peptide Library</topic><topic>Peptides - chemistry</topic><topic>Peptides - pharmacology</topic><topic>Phage-display</topic><topic>polypeptides</topic><topic>Solute Carrier Organic Anion Transporter Family Member 1b1</topic><topic>Solute Carrier Organic Anion Transporter Family Member 1B3</topic><topic>solutes</topic><topic>transporters</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arita, Yuko</creatorcontrib><creatorcontrib>Allen, Samantha</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Owen, Albert J.</creatorcontrib><creatorcontrib>Dentinger, Patrick</creatorcontrib><creatorcontrib>Sidhu, Sachdev S.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arita, Yuko</au><au>Allen, Samantha</au><au>Chen, Gang</au><au>Zhang, Wei</au><au>Wang, Ying</au><au>Owen, Albert J.</au><au>Dentinger, Patrick</au><au>Sidhu, Sachdev S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid isolation of peptidic inhibitors of the solute carrier family transporters OATP1B1 and OATP1B3 by cell-based phage display selections</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2016-04-29</date><risdate>2016</risdate><volume>473</volume><issue>2</issue><spage>370</spage><epage>376</epage><pages>370-376</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26792727</pmid><doi>10.1016/j.bbrc.2016.01.050</doi><tpages>7</tpages></addata></record> |
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subjects | 5â²CF 6â²CF 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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