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Abstract The structures and associated functions of biological molecules are driven by noncovalent interactions, which have classically been dominated by the hydrogen bond (H‐bond). Introduction of the σ‐hole concept to describe the anisotropic distribution of electrostatic potential of covalently bonded elements from across the periodic table has opened a broad range of nonclassical noncovalent ( nc NC) interactions for applications in chemistry and biochemistry. Here, we review how halogen bonds, chalcogen bonds and tetrel bonds, as they are found naturally or introduced synthetically, affect the structures, assemblies, and potential functions of peptides and proteins. This review intentionally focuses on examples that introduce or support principles of stability, assembly and catalysis that can potentially guide the design of new functional proteins. These three types of nc NC interactions have energies that are comparable to the H‐bond and, therefore, are now significant concepts in molecular recognition and design. However, the recently described H‐bond enhanced X‐bond shows how synergism among nc NC interactions can be exploited as potential means to broaden the range of their applications to affect protein structures and functions.
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A Biological Take on Halogen Bonding and Other Non‐Classical Non‐Covalent Interactions
Abstract Classical hydrogen bonds have, for many decades, been the dominant non‐covalent interaction in the toolbox that chemists and chemical engineers have used to design and control the structures of compounds and molecular assemblies as novel materials. Recently, a set of non‐classical non‐covalent (NC−NC) interactions have emerged that exploit the properties of the Group IV, V, VI, and VII elements of the periodic table (the tetrel, pnictogen, chalcogen, and halogen bonds, respectively). Our research group has been characterizing the prevalence, geometric constraints, and structure‐function relationship specifically of the halogen bond in biological systems. We have been particularly interested in exploiting the biological halogen bonds (or BXBs) to control the structures, stabilities, and activities of biomolecules, including the DNA Holliday junction and enzymes. In this review, we first provide a set of criteria for how to determine whether BXBs or any other NC−NC interactions would have biological relevance. We then navigate the trail of studies that had led us from an initial, very biological question to our current point in the journey to establish BXBs as a tool for biomolecular engineering. Finally, we close with a perspective on future directions for this line of research.
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- Award ID(s):
- 1905328
- PAR ID:
- 10239169
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- The Chemical Record
- Volume:
- 21
- Issue:
- 5
- ISSN:
- 1527-8999
- Page Range / eLocation ID:
- p. 1240-1251
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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