Sequence-Specific, Dynamic Covalent Crosslinking in Aqueous Media

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• 作者：Minfeng Li ; Kazuhiro Yamato ; Joseph S. Ferguson ; Kiran Kumar Singarapu ; Thomas Szyperski ; Bing Gong
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：January 16, 2008
• 年：2008
• 卷：130
• 期：2
• 页码：491 - 500
• 全文大小：214K
• 年卷期：v.130,no.2(January 16, 2008)
• ISSN：1520-5126

文摘

This article describes an associating system that integrates the specificity of multiple hydrogenbonding and the strength of dynamic covalent interactions. Linear oligoamides that sequence-specificallypair into H-bonded duplexes in nonpolar solvents were modified with S-trityl groups, allowing the reversibleformation of disulfide bonds. The disulfide-crosslinking reactions of oligoamides capable of pairing via two,four, and six intermolecular H-bonds, along with several control strands, were examined using ESI, MALDI-TOF, reverse phase HPLC, and two-dimensional NMR. Results from these studies demonstrate that thissystem possesses both the high fidelity of multiply H-bonded assemblies and the high stability of covalentinteraction, leading to the sequence-specific crosslinking of complementary oligoamides in not only nonpolar(methylene chloride) solutions but also highly competitive (aqueous) media. Experiments were designedto systematically probe the mechanism behind the specific formation of the sequence-matched products,which revealed a thermodymically controlled process. Multiple pairs in the same solution were crosslinkedin a sequence-specific fashion. In addition, a length-dependent selectivity was also observed. Thus,oligoamides with different lengths or sequences did not crosslink into mismatched products. As few as twoH-bonds is sufficient to bias the specific formation of the crosslinked product in aqueous media, suggestingthat associating units with tunable sizes, high stability, and high specificity can be conveniently designed.The combination of H-bonding and dynamic covalent interactions represents a new, generalizable strategyfor developing highly specific molecular associating units that are stable in a wide variety of media. Theseassociating units will greatly facilitate the construction of various structures with many applications.