Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries
© 2020 American Chemical Society. Nature has three biopolymers: oligonucleotides, polypeptides, and oligosaccharides. Each biopolymer has independent functions, but when needed, they form mixed assemblies for higher-order purposes, as in the case of ribosomal protein synthesis. Rather than forming l...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Chemical Society (ACS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/141200 |
| _version_ | 1826195474144559104 |
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| author | Pomplun, Sebastian Gates, Zachary P Zhang, Genwei Quartararo, Anthony J Pentelute, Bradley L |
| author_facet | Pomplun, Sebastian Gates, Zachary P Zhang, Genwei Quartararo, Anthony J Pentelute, Bradley L |
| author_sort | Pomplun, Sebastian |
| collection | MIT |
| description | © 2020 American Chemical Society. Nature has three biopolymers: oligonucleotides, polypeptides, and oligosaccharides. Each biopolymer has independent functions, but when needed, they form mixed assemblies for higher-order purposes, as in the case of ribosomal protein synthesis. Rather than forming large complexes to coordinate the role of different biopolymers, we dovetail protein amino acids and nucleobases into a single low molecular weight precision polyamide polymer. We established efficient chemical synthesis and de novo sequencing procedures and prepared combinatorial libraries with up to 100 million biohybrid molecules. This biohybrid material has a higher bulk affinity to oligonucleotides than peptides composed exclusively of canonical amino acids. Using affinity selection mass spectrometry, we discovered variants with a high affinity for pre-microRNA hairpins. Our platform points toward the development of high throughput discovery of sequence defined polymers with designer properties, such as oligonucleotide binding. |
| first_indexed | 2024-09-23T10:13:14Z |
| format | Article |
| id | mit-1721.1/141200 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:13:14Z |
| publishDate | 2022 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1412002022-03-16T03:32:16Z Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries Pomplun, Sebastian Gates, Zachary P Zhang, Genwei Quartararo, Anthony J Pentelute, Bradley L © 2020 American Chemical Society. Nature has three biopolymers: oligonucleotides, polypeptides, and oligosaccharides. Each biopolymer has independent functions, but when needed, they form mixed assemblies for higher-order purposes, as in the case of ribosomal protein synthesis. Rather than forming large complexes to coordinate the role of different biopolymers, we dovetail protein amino acids and nucleobases into a single low molecular weight precision polyamide polymer. We established efficient chemical synthesis and de novo sequencing procedures and prepared combinatorial libraries with up to 100 million biohybrid molecules. This biohybrid material has a higher bulk affinity to oligonucleotides than peptides composed exclusively of canonical amino acids. Using affinity selection mass spectrometry, we discovered variants with a high affinity for pre-microRNA hairpins. Our platform points toward the development of high throughput discovery of sequence defined polymers with designer properties, such as oligonucleotide binding. 2022-03-15T18:49:38Z 2022-03-15T18:49:38Z 2020 2022-03-15T18:46:14Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141200 Pomplun, Sebastian, Gates, Zachary P, Zhang, Genwei, Quartararo, Anthony J and Pentelute, Bradley L. 2020. "Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries." Journal of the American Chemical Society, 142 (46). en 10.1021/JACS.0C08964 Journal of the American Chemical Society Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Pomplun, Sebastian Gates, Zachary P Zhang, Genwei Quartararo, Anthony J Pentelute, Bradley L Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries |
| title | Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries |
| title_full | Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries |
| title_fullStr | Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries |
| title_full_unstemmed | Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries |
| title_short | Discovery of Nucleic Acid Binding Molecules from Combinatorial Biohybrid Nucleobase Peptide Libraries |
| title_sort | discovery of nucleic acid binding molecules from combinatorial biohybrid nucleobase peptide libraries |
| url | https://hdl.handle.net/1721.1/141200 |
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