Boron Mimetics: 1,2‐Dihydro‐1,2‐azaborines Bind inside a Nonpolar Cavity of T4 Lysozyme

Liu, Lijun; Marwitz, Adam J. V.; Matthews, Brian W.; Liu, Shih‐Yuan

doi:10.1002/anie.200903390

Cited by 118 publications

(61 citation statements)

References 43 publications

(25 reference statements)

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“…51 Recently, it has been shown that 1,2-azaborine and 1-ethyl-1,2-dihydro-1,2-azaborine also bind. 52 These novel analogs provide a way to incorporate boron into compounds of biomedical interest. The L99A cavity also binds halogenated benzenes, such as C 6 F 6 , C 6 H 5 I, and C 6 F 5 I, among others.…”

Section: Engineered Ligand Binding Sitesmentioning

confidence: 99%

Lessons from the lysozyme of phage T4

et al. 2010

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An overview is presented of some of the major insights that have come from studies of the structure, stability, and folding of T4 phage lysozyme. A major purpose of this review is to provide the reader with a complete tabulation of all of the variants that have been characterized, including melting temperatures, crystallographic data, Protein Data Bank access codes, and references to the original literature. The greatest increase in melting temperature (T m ) for any point mutant is 5.1°C for the mutant Ser 117 fi Val. This is achieved in part not only by hydrophobic stabilization but also by eliminating an unusually short hydrogen bond of 2.48 Å that apparently has an unfavorable van der Waals contact. Increases in T m of more than 3-4°C for point mutants are rare, whereas several different types of destabilizing substitutions decrease T m by 20°C or thereabouts. The energetic cost of cavity creation and its relation to the hydrophobic effect, derived from early studies of ''large-tosmall'' mutants in the core of T4 lysozyme, has recently been strongly supported by related studies of the intrinsic membrane protein bacteriorhodopsin. The L99A cavity in the C-terminal domain of the protein, which readily binds benzene and many other ligands, has been the subject of extensive study. Crystallographic evidence, together with recent NMR analysis, suggest that these ligands are admitted by a conformational change involving Helix F and its neighbors. A total of 43 nonisomorphous crystal forms of different monomeric lysozyme mutants were obtained plus three more for synthetically-engineered dimers. Among the 43 space groups, P2 1 2 1 2 1 and P2 1 were observed most frequently, consistent with the prediction of Wukovitz and Yeates.

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Section: Engineered Ligand Binding Sitesmentioning

confidence: 99%

Lessons from the lysozyme of phage T4

et al. 2010

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“…The demonstration of the binding of 1,2-azaborines inside the cavity of a lysozyme suggests that certain boron-containing compounds have the ability to serve as hydrophobic arene mimics in biological systems. [148] The pharmacological effect of the replacement of carbon by silicon in certain drugs is also an area of intense investigation. [ phosphazene polymers may presage their future applications as biomedical materials.…”

Section: Medicinal Chemistrymentioning

confidence: 99%

The Future of Main Group Chemistry

Chivers

Konu

2009

Comments on Inorganic Chemistry

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After a brief reflection on the important discoveries in main group chemistry during the past century, this article provides some suggestions concerning areas in which studies of s-and p-block element compounds are likely to have a major impact on the discipline of chemistry and upon society in general in the context of significant advances that have been made in the last decade. These areas range from fundamental to applied aspects of the subject. In the former category, novel aspects of chemical bonding and new reagents for synthetic applications are considered. From a more practical perspective alternative energy sources (especially hydrogen storage), new materials (notably nanomaterials and chemical sensors), catalysis (in the context of green chemistry), and medicinal chemistry (both diagnostic and therapeutic applications) are discussed.

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“…In the nonpolar cavity (L99A), X-ray crystallographic analysis of the protein–ligand complexes revealed that 1,2-azaborines and their carbonaceous counterparts bind similarly 8 (Figure 3, top row). In complexes with ethyl-substituted ligands, two conformations are observed (also seen in the complexes EtBnz@L99A/M102Q and BEtAb@L99A/M102Q), and the ethyl substituent is positioned in the bulge region of the cavity, presumably due to geometric complementarity.…”

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Hydrogen Bonding of 1,2-Azaborines in the Binding Cavity of T4 Lysozyme Mutants: Structures and Thermodynamics

et al. 2016

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Protein crystallography and calorimetry were used to characterize the binding of 1,2-azaborines to model cavities in T4 lysozyme in direct comparison to their carbonaceous counterparts. In the apolar L99A cavity, affinity for Ab dropped only slightly versus benzene. In the cavity designed to accommodate a single hydrogen bond (L99A/M102Q), Gln102=O⋯H—N hydrogen bonding for Ab and BEtAb was observed in the crystallographic complexes. The strength of the hydrogen bonding was estimated as 0.94 and 0.64 kcal/mol for Ab and BEtAb, respectively. This work unambiguously demonstrates that 1,2-azaborines can be readily accommodated in classic aryl recognition pockets and establishes one of 1,2-azaborine’s distinguishing features from its carbonaceous isostere benzene: its ability to serve as an NH hydrogen bond donor in a biological setting.

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Boron Mimetics: 1,2‐Dihydro‐1,2‐azaborines Bind inside a Nonpolar Cavity of T4 Lysozyme

Cited by 118 publications

References 43 publications

Lessons from the lysozyme of phage T4

Lessons from the lysozyme of phage T4

The Future of Main Group Chemistry

Hydrogen Bonding of 1,2-Azaborines in the Binding Cavity of T4 Lysozyme Mutants: Structures and Thermodynamics

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