Article | Published:

Enzyme-free translation of DNA into sequence-defined synthetic polymers structurally unrelated to nucleic acids

Nature Chemistry volume 5, pages 282292 (2013) | Download Citation

Abstract

The translation of DNA sequences into corresponding biopolymers enables the production, function and evolution of the macromolecules of life. In contrast, methods to generate sequence-defined synthetic polymers with similar levels of control have remained elusive. Here, we report the development of a DNA-templated translation system that enables the enzyme-free translation of DNA templates into sequence-defined synthetic polymers that have no necessary structural relationship with nucleic acids. We demonstrate the efficiency, sequence-specificity and generality of this translation system by oligomerizing building blocks including polyethylene glycol, α-(D)-peptides, and β-peptides in a DNA-programmed manner. Sequence-defined synthetic polymers with molecular weights of 26 kDa containing 16 consecutively coupled building blocks and 90 densely functionalized β-amino acid residues were translated from DNA templates using this strategy. We integrated the DNA-templated translation system developed here into a complete cycle of translation, coding sequence replication, template regeneration and re-translation suitable for the iterated in vitro selection of functional sequence-defined synthetic polymers unrelated in structure to nucleic acids.

  • Compound C117H183N45O37S4

    (S)-2-Amino-N-((S)-3-amino-2-(3-((51S,100S)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63,81,87-tris(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-aminobutyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)-3-oxopropyl)-3-hydroxypropanamide

  • Compound C119H186N46O39S4

    (S)-2-Amino-N-((S)-3-amino-2-(3-((51S,100S)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63,81,87-tris(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-(2-(aminooxy)acetamido)butyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)-3-oxopropyl)-3-hydroxypropanamide

  • Compound C119H187N47O38S4

    (S)-2-Amino-N-((S)-3-amino-2-(3-((51S,100S)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63,81,87-tris(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-(2-hydrazinylacetamido)butyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)-3-oxopropyl)-3-hydroxypropanamide

  • Compound C118H179N45O35S4

    (S)-2-(3-((51S,100S)-69,75-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63,81,87-tris(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)hept-6-ynamide

  • Compound C115H174N38O43S4

    N-((S)-1-Amino-1-oxo-3-(2-oxoacetamido)propan-2-yl)-3-((51S,100S)-81,87-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-75-(2-(6-amino-9H-purin-9-yl)acetyl)-63,69-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-51-((2-oxoacetamido)methyl)-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamide

  • Compound C117H182N42O39S4

    (S)-6-Azido-2-(3-((51S,100S)-81,87-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-75-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-63,69-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)hexanamide

  • Compound C109H166N42O35S4

    (S)-6-Azido-2-(3-((39S,88S)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63-(2-(6-amino-9H-purin-9-yl)acetyl)-39-(4-azidobutyl)-51,57-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-88-yl)propanamido)hexanamide

  • Compound C82H113N41O22S4

    (S)-6-Azido-2-(3-((45S,48S)-26,32-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-20-(2-(6-amino-9H-purin-9-yl)acetyl)-48-(4-azidobutyl)-8,14-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,12,18,24,30,36,44,47,50-nonaoxo-1,2,39,40-tetrathia-5,8,11,14,17,20,23,26,29,32,35,43,46,49-tetradecaazacyclodopentacontan-45-yl)propanamido)hexanamide

  • Compound C93H134N42O27S4

    (S)-6-Azido-2-(3-((15S,64S)-45,51-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-39-(2-(6-amino-9H-purin-9-yl)acetyl)-15-(4-azidobutyl)-27,33-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-14,17,25,31,37,43,49,55,63,66-decaoxo-1,4,7,10-tetraoxa-20,21,58,59-tetrathia-13,16,24,27,30,33,36,39,42,45,48,51,54,62,65-pentadecaazacyclooctahexacontan-64-yl)propanamido)hexanamide

  • Compound C104H155N43O32S4

    (S)-6-Azido-2-(3-((15S,64S)-45,51-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-33-(2-(6-amino-9H-purin-9-yl)acetyl)-15-(4-azidobutyl)-27,39-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-14,17,25,31,37,43,49,55,63,66,82-undecaoxo-1,4,7,10,69,72,75,78-octaoxa-20,21,58,59-tetrathia-13,16,24,27,30,33,36,39,42,45,48,51,54,62,65,81-hexadecaazacyclotetraoctacontan-64-yl)propanamido)hexanamide

  • Compound C131H208N44O45S4

    N-((S)-6-Amino-5-(3-((39S,88S)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63-(2-(6-amino-9H-purin-9-yl)acetyl)-39-(1-azido-15-oxo-3,6,9,12-tetraoxa-16-azaicosan-20-yl)-51,57-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-88-yl)propanamido)-6-oxohexyl)-1-azido-3,6,9,12-tetraoxapentadecan-15-amide

  • Compound C117H186N38O39S4

    (S)-6-Amino-2-(3-((51S,100S)-81,87-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-69-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-aminobutyl)-63,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)hexanamide

  • Compound C121H192N40O43S4

    (S)-6-(2-(Aminooxy)acetamido)-2-(3-((51S,100S)-81,87-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-69-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-(2-(aminooxy)acetamido)butyl)-63,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)hexanamide

  • Compound C121H194N42O41S4

    (S)-2-(3-((51S,100S)-81,87-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-69-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-(2-hydrazinylacetamido)butyl)-63,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)-6-(2-hydrazinylacetamido)hexanamide

  • Compound C127H194N38O41S4

    (S)-2-(3-((51S,100S)-81,87-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-69-(2-(6-amino-9H-purin-9-yl)acetyl)-63,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-51-(4-(pent-4-ynamido)butyl)-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)-6-(pent-4-ynamido)hexanamide

  • Compound C137H214N38O47S4

    N-((S)-6-Amino-5-(3-((39S,88S)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-57-(2-(6-amino-9H-purin-9-yl)acetyl)-51,63-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-39-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-88-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C113H166N38O35S4

    (S)-2-(3-((27S,76S)-57,63-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-45-(2-(6-amino-9H-purin-9-yl)acetyl)-39,51-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-26,29,37,43,49,55,61,67,75,78-decaoxo-27-(4-(3-(prop-2-yn-1-yloxy)propanamido)butyl)-1,4,7,10,13,16,19,22-octaoxa-32,33,70,71-tetrathia-25,28,36,39,42,45,48,51,54,57,60,63,66,74,77-pentadecaazacyclooctacontan-76-yl)propanamido)-6-(3-(prop-2-yn-1-yloxy)propanamido)hexanamide

  • Compound C94H129N37O26S4

    (S)-2-(3-((45S,48S)-26,32-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-14-(2-(6-amino-9H-purin-9-yl)acetyl)-8,20-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,12,18,24,30,36,44,47,50-nonaoxo-48-(4-(3-(prop-2-yn-1-yloxy)propanamido)butyl)-1,2,39,40-tetrathia-5,8,11,14,17,20,23,26,29,32,35,43,46,49-tetradecaazacyclodopentacontan-45-yl)propanamido)-6-(3-(prop-2-yn-1-yloxy)propanamido)hexanamide

  • Compound C110H161N37O34S4

    N-((S)-6-Amino-5-(3-((45S,48S)-26,32-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-14-(2-(6-amino-9H-purin-9-yl)acetyl)-8,20-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,12,18,24,30,36,44,47,50-nonaoxo-48-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,2,39,40-tetrathia-5,8,11,14,17,20,23,26,29,32,35,43,46,49-tetradecaazacyclodopentacontan-45-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C105H150N38O31S4

    (S)-2-(3-((15S,64S)-45,51-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-33-(2-(6-amino-9H-purin-9-yl)acetyl)-27,39-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-14,17,25,31,37,43,49,55,63,66-decaoxo-15-(4-(3-(prop-2-yn-1-yloxy)propanamido)butyl)-1,4,7,10-tetraoxa-20,21,58,59-tetrathia-13,16,24,27,30,33,36,39,42,45,48,51,54,62,65-pentadecaazacyclooctahexacontan-64-yl)propanamido)-6-(3-(prop-2-yn-1-yloxy)propanamido)hexanamide

  • Compound C121H182N38O39S4

    N-((S)-6-Amino-5-(3-((15S,64S)-45,51-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-33-(2-(6-amino-9H-purin-9-yl)acetyl)-27,39-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-14,17,25,31,37,43,49,55,63,66-decaoxo-15-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,4,7,10-tetraoxa-20,21,58,59-tetrathia-13,16,24,27,30,33,36,39,42,45,48,51,54,62,65-pentadecaazacyclooctahexacontan-64-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C129H198N38O43S4

    N-((S)-6-Amino-5-(3-((27S,76S)-57,63-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-45-(2-(6-amino-9H-purin-9-yl)acetyl)-39,51-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-26,29,37,43,49,55,61,67,75,78-decaoxo-27-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,4,7,10,13,16,19,22-octaoxa-32,33,70,71-tetrathia-25,28,36,39,42,45,48,51,54,57,60,63,66,74,77-pentadecaazacyclooctacontan-76-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C146H221N49O46S4

    N-((S)-6-Amino-5-(3-((45S,96S)-26,32-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-14-(2-(6-amino-9H-purin-9-yl)acetyl)-8,20-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,12,18,24,30,36,44,47,51,55,59,63,67,71,75,79,83,87,91,95,98-henicosaoxo-96-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,2,39,40-tetrathia-5,8,11,14,17,20,23,26,29,32,35,43,46,50,54,58,62,66,70,74,78,82,86,90,94,97-hexacosaazacyclohectan-45-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C157H229N53O52S4

    3-((7S,19R,31R,34R,46R,58S)-88,94-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-76-(2-(6-amino-9H-purin-9-yl)acetyl)-46-benzyl-7-((S)-25-carbamoyl-19,27-dioxo-4,7,10,13,16-pentaoxa-20,26-diazanonacos-1-yn-29-yl)-31-isobutyl-19-methyl-70,82-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60,68,74,80,86,92,98-pentacosaoxo-58-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,2,63,64-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,67,70,73,76,79,82,85,88,91,94,97-triacontaazacyclohectan-34-yl)propanoic acid

  • Compound C130H192N58O38S4

    (S)-6-Azido-2-(3-((7S,19R,31R,34R,46R,58S)-88,94-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-82-(2-(6-amino-9H-purin-9-yl)acetyl)-34-(4-aminobutyl)-58-(4-azidobutyl)-46-(cyclohexylmethyl)-31-isobutyl-19-methyl-70,76-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60,68,74,80,86,92,98-pentacosaoxo-1,2,63,64-tetrathia-5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53,56,59,67,70,73,76,79,82,85,88,91,94,97-triacontaazacyclohectan-7-yl)propanamido)hexanamide

  • Compound C117H182N42O39S4

    (S)-6-Azido-2-(3-((51S,100S)-81,87-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-69,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)hexanamide

  • Compound C137H214N38O47S4

    N-((S)-6-Amino-5-(3-((39S,88S)-57,69-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-51-(2-(6-amino-9H-purin-9-yl)acetyl)-63,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-39-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-88-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C117H182N42O39S4

    (S)-6-Azido-2-(3-((51S,100S)-69,87-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-75-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-63,81-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamido)hexanamide

  • Compound C137H214N38O47S4

    N-((S)-6-Amino-5-(3-((39S,88S)-51,69-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63-(2-(6-amino-9H-purin-9-yl)acetyl)-57,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-39-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-88-yl)propanamido)-6-oxohexyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C110H168N34O41S4

    3,3'-((51S,100S)-81,87-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-75-(2-(6-amino-9H-purin-9-yl)acetyl)-63,69-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectane-51,100-diyl)dipropanoic acid

  • Compound C111H171N41O35S4

    3-((51S,100S)-69,75-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63,81,87-tris(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-aminobutyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanoic acid

  • Compound C129H179N49O32S4

    3,3'-((45S,49S,53R,57S,61S,65S,69S,72S)-61-((1H-Indol-3-yl)methyl)-45-(3-(((S)-1-amino-6-azido-1-oxohexan-2-yl)amino)-3-oxopropyl)-26,32-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-20-(2-(6-amino-9H-purin-9-yl)acetyl)-49-(4-aminobutyl)-72-(4-azidobutyl)-69-benzyl-53-isopropyl-8,14-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,12,18,24,30,36,44,47,51,55,59,63,67,71,74-pentadecaoxo-1,2,39,40-tetrathia-5,8,11,14,17,20,23,26,29,32,35,43,46,50,54,58,62,66,70,73-icosaazacyclohexaheptacontane-57,65-diyl)dipropanoic acid

  • Compound C139H196N44O35S4

    3-((45S,49R,53S,57S,61R,65S,69S,72S)-45-(3-(((S)-1-Amino-1-oxo-6-(3-(prop-2-yn-1-yloxy)propanamido)hexan-2-yl)amino)-3-oxopropyl)-26,32-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-14-(2-(6-amino-9H-purin-9-yl)acetyl)-65-(4-aminobutyl)-69-benzyl-57-(4-hydroxybenzyl)-49,61-diisopropyl-8,20-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-6,12,18,24,30,36,44,47,51,55,59,63,67,71,74-pentadecaoxo-72-(4-(3-(prop-2-yn-1-yloxy)propanamido)butyl)-1,2,39,40-tetrathia-5,8,11,14,17,20,23,26,29,32,35,43,46,50,54,58,62,66,70,73-icosaazacyclohexaheptacontan-53-yl)propanoic acid

  • Compound C117H184N42O40S4

    (47S,102S)-1-Amino-102-(3-(((S)-1-amino-6-azido-1-oxohexan-2-yl)amino)-3-oxopropyl)-11,17-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-23-(2-(6-amino-9H-purin-9-yl)acetyl)-47-(4-azidobutyl)-29,35-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-7,13,19,25,31,37,45,48,100-nonaoxo-52,55,58,61,64,67,70,73,76,79,82,85,88,91,94,97-hexadecaoxa-3,4,41,42-tetrathia-8,11,14,17,20,23,26,29,32,35,38,46,49,101-tetradecaazatrihectan-103-oic acid

  • Compound C139H218N38O49S4

    (50S,93S)-14,20-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-32-(2-(6-amino-9H-purin-9-yl)acetyl)-93-((S)-25-carbamoyl-19,27-dioxo-4,7,10,13,16-pentaoxa-20,26-diazanonacos-1-yn-29-yl)-26,38-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-2,10,16,22,28,34,40,48,51,91-decaoxo-50-(19-oxo-4,7,10,13,16-pentaoxa-20-azatetracos-1-yn-24-yl)-55,58,61,64,67,70,73,76,79,82,85,88-dodecaoxa-6,7,44,45-tetrathia-3,11,14,17,20,23,26,29,32,35,38,41,49,52,92-pentadecaazatetranonacontan-94-oic acid

  • Compound C111H172N38O38S4

    3-((51S,100S)-81,87-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-75-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-63,69-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamide

  • Compound C117H180N36O40S4

    N-(4-((39S,88S)-88-(3-Amino-3-oxopropyl)-69,75-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-57-(2-(6-amino-9H-purin-9-yl)acetyl)-51,63-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-39-yl)butyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C111H172N38O38S4

    3-((51S,100S)-81,87-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-69,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamide

  • Compound C117H180N36O40S4

    N-(4-((39S,88S)-88-(3-Amino-3-oxopropyl)-57,69-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-51-(2-(6-amino-9H-purin-9-yl)acetyl)-63,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-39-yl)butyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C111H172N38O38S4

    3-((51S,100S)-69,87-Bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-75-(2-(6-amino-9H-purin-9-yl)acetyl)-51-(4-azidobutyl)-63,81-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-50,53,61,67,73,79,85,91,99,102-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34,37,40,43,46-hexadecaoxa-56,57,94,95-tetrathia-49,52,60,63,66,69,72,75,78,81,84,87,90,98,101-pentadecaazacyclotetrahectan-100-yl)propanamide

  • Compound C117H180N36O40S4

    N-(4-((39S,88S)-88-(3-Amino-3-oxopropyl)-51,69-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-63-(2-(6-amino-9H-purin-9-yl)acetyl)-57,75-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-38,41,49,55,61,67,73,79,87,90-decaoxo-1,4,7,10,13,16,19,22,25,28,31,34-dodecaoxa-44,45,82,83-tetrathia-37,40,48,51,54,57,60,63,66,69,72,75,78,86,89-pentadecaazacyclodononacontan-39-yl)butyl)-4,7,10,13,16-pentaoxanonadec-18-yn-1-amide

  • Compound C93H132N36O28S4

    N-(4-((15S,64S)-64-(3-Amino-3-oxopropyl)-27,45-bis(2-(2-amino-6-oxo-1H-purin-9(6H)-yl)acetyl)-39-(2-(6-amino-9H-purin-9-yl)acetyl)-33,51-bis(2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetyl)-14,17,25,31,37,43,49,55,63,66-decaoxo-1,4,7,10-tetraoxa-20,21,58,59-tetrathia-13,16,24,27,30,33,36,39,42,45,48,51,54,62,65-pentadecaazacyclooctahexacontan-15-yl)butyl)-3-(prop-2-yn-1-yloxy)propanamide

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Acknowledgements

This work was supported by the Howard Hughes Medical Institute and the NIH/NIGMS (R01GM065865). J.N. was partially supported by an Eli Lilly Organic Chemistry Graduate Fellowship. R.H. was supported by a postdoctoral fellowship from Canada's National Science and Engineering Council (NSERC). The authors are grateful to J. Heemstra, Y. Brudno, C. Dumelin, Y. Lu and S. Trauger for helpful discussions.

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  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA

    • Jia Niu
    • , Ryan Hili
    •  & David R. Liu

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Contributions

J.N., R.H. and D.R.L. designed the research, analysed the data and co-wrote the manuscript. J.N. performed the experiments.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David R. Liu.

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https://doi.org/10.1038/nchem.1577

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