Side chain determinants of biopolymer function during selection and replication
The chemical functionalities within biopolymers determine their physical properties and biological activities. The relationship between the side chains available to a biopolymer population and the potential functions of the resulting polymers, however, has proven difficult to study experimentally. U...
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| Veröffentlicht in: | Nature chemical biology 2019-04, Vol.15 (4), p.419-426 |
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| creator | Lichtor, Phillip A. Chen, Zhen Elowe, Nadine H. Chen, Jonathan C. Liu, David R. |
| description | The chemical functionalities within biopolymers determine their physical properties and biological activities. The relationship between the side chains available to a biopolymer population and the potential functions of the resulting polymers, however, has proven difficult to study experimentally. Using seven sets of chemically diverse charged, polar, and nonpolar side chains, we performed cycles of artificial translation, in vitro selections for binding to either PCSK9 or IL-6 protein, and replication on libraries of random side chain-functionalized nucleic acid polymers. Polymer sequence convergence, bulk population target binding, affinity of individual polymers, and head-to-head competition among post-selection libraries collectively indicate that polymer libraries with nonpolar side chains outperformed libraries lacking these side chains. The presence of nonpolar groups, resembling functionality existing in proteins but missing from natural nucleic acids, thus may be strong determinants of binding activity. This factor may contribute to the apparent evolutionary advantage of proteins over their nucleic acid precursors for some molecular recognition tasks.
A comprehensive analysis of the effect of the side chain composition of nucleic acid polymers revealed that the polarity of the side chains determines the performance of polymers during in vitro selections for protein binding. |
| doi_str_mv | 10.1038/s41589-019-0229-2 |
| format | Article |
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A comprehensive analysis of the effect of the side chain composition of nucleic acid polymers revealed that the polarity of the side chains determines the performance of polymers during in vitro selections for protein binding.</description><identifier>ISSN: 1552-4450</identifier><identifier>EISSN: 1552-4469</identifier><identifier>DOI: 10.1038/s41589-019-0229-2</identifier><identifier>PMID: 30742124</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/92/147 ; 631/92/2132 ; 631/92/552 ; 631/92/610 ; Binding ; Biochemical Engineering ; Biochemistry ; Biological properties ; Bioorganic Chemistry ; Biopolymers ; Biopolymers - chemistry ; Biopolymers - physiology ; Cell Biology ; Chemistry ; Chemistry and Materials Science ; Chemistry/Food Science ; Determinants ; DNA Replication ; Humans ; Interleukin 6 ; Interleukin-6 - chemistry ; Libraries ; Nucleic acids ; Organic chemistry ; Peptide Library ; Physical properties ; Polymers ; Polymers - chemistry ; Proprotein Convertase 9 - chemistry ; Proteins ; Proteins - chemistry ; Replication</subject><ispartof>Nature chemical biology, 2019-04, Vol.15 (4), p.419-426</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2019</rights><rights>2019© The Author(s), under exclusive licence to Springer Nature America, Inc. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-5792290791ded27816bed05b0f54ae0e827ab8c69a9d3ee8614cb988cc83ad4a3</citedby><cites>FETCH-LOGICAL-c470t-5792290791ded27816bed05b0f54ae0e827ab8c69a9d3ee8614cb988cc83ad4a3</cites><orcidid>0000-0003-0066-1354 ; 0000-0003-4346-0501 ; 0000-0002-9943-7557</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41589-019-0229-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41589-019-0229-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30742124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lichtor, Phillip A.</creatorcontrib><creatorcontrib>Chen, Zhen</creatorcontrib><creatorcontrib>Elowe, Nadine H.</creatorcontrib><creatorcontrib>Chen, Jonathan C.</creatorcontrib><creatorcontrib>Liu, David R.</creatorcontrib><title>Side chain determinants of biopolymer function during selection and replication</title><title>Nature chemical biology</title><addtitle>Nat Chem Biol</addtitle><addtitle>Nat Chem Biol</addtitle><description>The chemical functionalities within biopolymers determine their physical properties and biological activities. The relationship between the side chains available to a biopolymer population and the potential functions of the resulting polymers, however, has proven difficult to study experimentally. Using seven sets of chemically diverse charged, polar, and nonpolar side chains, we performed cycles of artificial translation, in vitro selections for binding to either PCSK9 or IL-6 protein, and replication on libraries of random side chain-functionalized nucleic acid polymers. Polymer sequence convergence, bulk population target binding, affinity of individual polymers, and head-to-head competition among post-selection libraries collectively indicate that polymer libraries with nonpolar side chains outperformed libraries lacking these side chains. The presence of nonpolar groups, resembling functionality existing in proteins but missing from natural nucleic acids, thus may be strong determinants of binding activity. This factor may contribute to the apparent evolutionary advantage of proteins over their nucleic acid precursors for some molecular recognition tasks.
A comprehensive analysis of the effect of the side chain composition of nucleic acid polymers revealed that the polarity of the side chains determines the performance of polymers during in vitro selections for protein binding.</description><subject>631/92/147</subject><subject>631/92/2132</subject><subject>631/92/552</subject><subject>631/92/610</subject><subject>Binding</subject><subject>Biochemical Engineering</subject><subject>Biochemistry</subject><subject>Biological properties</subject><subject>Bioorganic Chemistry</subject><subject>Biopolymers</subject><subject>Biopolymers - chemistry</subject><subject>Biopolymers - physiology</subject><subject>Cell Biology</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chemistry/Food Science</subject><subject>Determinants</subject><subject>DNA Replication</subject><subject>Humans</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - chemistry</subject><subject>Libraries</subject><subject>Nucleic acids</subject><subject>Organic chemistry</subject><subject>Peptide Library</subject><subject>Physical properties</subject><subject>Polymers</subject><subject>Polymers - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature chemical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lichtor, Phillip A.</au><au>Chen, Zhen</au><au>Elowe, Nadine H.</au><au>Chen, Jonathan C.</au><au>Liu, David R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Side chain determinants of biopolymer function during selection and replication</atitle><jtitle>Nature chemical biology</jtitle><stitle>Nat Chem Biol</stitle><addtitle>Nat Chem Biol</addtitle><date>2019-04-01</date><risdate>2019</risdate><volume>15</volume><issue>4</issue><spage>419</spage><epage>426</epage><pages>419-426</pages><issn>1552-4450</issn><eissn>1552-4469</eissn><abstract>The chemical functionalities within biopolymers determine their physical properties and biological activities. The relationship between the side chains available to a biopolymer population and the potential functions of the resulting polymers, however, has proven difficult to study experimentally. Using seven sets of chemically diverse charged, polar, and nonpolar side chains, we performed cycles of artificial translation, in vitro selections for binding to either PCSK9 or IL-6 protein, and replication on libraries of random side chain-functionalized nucleic acid polymers. Polymer sequence convergence, bulk population target binding, affinity of individual polymers, and head-to-head competition among post-selection libraries collectively indicate that polymer libraries with nonpolar side chains outperformed libraries lacking these side chains. The presence of nonpolar groups, resembling functionality existing in proteins but missing from natural nucleic acids, thus may be strong determinants of binding activity. This factor may contribute to the apparent evolutionary advantage of proteins over their nucleic acid precursors for some molecular recognition tasks.
A comprehensive analysis of the effect of the side chain composition of nucleic acid polymers revealed that the polarity of the side chains determines the performance of polymers during in vitro selections for protein binding.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>30742124</pmid><doi>10.1038/s41589-019-0229-2</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0066-1354</orcidid><orcidid>https://orcid.org/0000-0003-4346-0501</orcidid><orcidid>https://orcid.org/0000-0002-9943-7557</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/92/147 631/92/2132 631/92/552 631/92/610 Binding Biochemical Engineering Biochemistry Biological properties Bioorganic Chemistry Biopolymers Biopolymers - chemistry Biopolymers - physiology Cell Biology Chemistry Chemistry and Materials Science Chemistry/Food Science Determinants DNA Replication Humans Interleukin 6 Interleukin-6 - chemistry Libraries Nucleic acids Organic chemistry Peptide Library Physical properties Polymers Polymers - chemistry Proprotein Convertase 9 - chemistry Proteins Proteins - chemistry Replication |
| title | Side chain determinants of biopolymer function during selection and replication |
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