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      Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation

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          Abstract

          Designing artificial macromolecules with absolute sequence order represents a considerable challenge. Here we report an advanced light-induced avenue to monodisperse sequence-defined functional linear macromolecules up to decamers via a unique photochemical approach. The versatility of the synthetic strategy—combining sequential and modular concepts—enables the synthesis of perfect macromolecules varying in chemical constitution and topology. Specific functions are placed at arbitrary positions along the chain via the successive addition of monomer units and blocks, leading to a library of functional homopolymers, alternating copolymers and block copolymers. The in-depth characterization of each sequence-defined chain confirms the precision nature of the macromolecules. Decoding of the functional information contained in the molecular structure is achieved via tandem mass spectrometry without recourse to their synthetic history, showing that the sequence information can be read. We submit that the presented photochemical strategy is a viable and advanced concept for coding individual monomer units along a macromolecular chain.

          Abstract

          Controlling the molecular sequence of polymers and oligomers is a challenging task. Here the authors use a photoligation approach to synthesise macromolecules with functionality at defined positions throughout the chain, and additionally decode the sequence information via tandem mass spectrometry.

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          Most cited references16

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          The protein-folding problem, 50 years on.

          The protein-folding problem was first posed about one half-century ago. The term refers to three broad questions: (i) What is the physical code by which an amino acid sequence dictates a protein's native structure? (ii) How can proteins fold so fast? (iii) Can we devise a computer algorithm to predict protein structures from their sequences? We review progress on these problems. In a few cases, computer simulations of the physical forces in chemically detailed models have now achieved the accurate folding of small proteins. We have learned that proteins fold rapidly because random thermal motions cause conformational changes leading energetically downhill toward the native structure, a principle that is captured in funnel-shaped energy landscapes. And thanks in part to the large Protein Data Bank of known structures, predicting protein structures is now far more successful than was thought possible in the early days. What began as three questions of basic science one half-century ago has now grown into the full-fledged research field of protein physical science.
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            "Clicking" polymers or just efficient linking: what is the difference?

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              Iterative exponential growth of stereo- and sequence-controlled polymers.

              Chemists have long sought sequence-controlled synthetic polymers that mimic nature's biopolymers, but a practical synthetic route that enables absolute control over polymer sequence and structure remains a key challenge. Here, we report an iterative exponential growth plus side-chain functionalization (IEG+) strategy that begins with enantiopure epoxides and facilitates the efficient synthesis of a family of uniform >3 kDa macromolecules of varying sequence and stereoconfiguration that are coupled to produce unimolecular polymers (>6 kDa) with sequences and structures that cannot be obtained using traditional polymerization techniques. Selective side-chain deprotection of three hexadecamers is also demonstrated, which imbues each compound with the ability to dissolve in water. We anticipate that these new macromolecules and the general IEG+ strategy will find broad application as a versatile platform for the scalable synthesis of sequence-controlled polymers.
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                Author and article information

                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group
                2041-1723
                30 November 2016
                2016
                : 7
                : 13672
                Affiliations
                [1 ]Soft Matter Synthesis Laboratory, Institut für Biologische Grenzflächen, Karlsruhe Institute of Technology (KIT) , Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
                [2 ]Preparative Macromolecular Chemistry, Institut für Technische Chemie und Polymerchemie, Karlsruhe Institute of Technology (KIT) , Engesserstrasse 18, 76131 Karlsruhe, Germany
                [3 ]Department of Molecular Biophysics (IGB-2), Institut für Biologische Grenzflächen, Karlsruhe Institute of Technology (KIT) , Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
                [4 ]BAM-Federal Institute for Materials Research and Testing , Richard-Willstätter-Strasse 11, 12489 Berlin, Germany
                Author notes
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-2356-4226
                Article
                ncomms13672
                10.1038/ncomms13672
                5141382
                27901024
                0e930567-d25c-48ce-a7d1-273c2ca8fb0b
                Copyright © 2016, The Author(s)

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 17 August 2016
                : 23 October 2016
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