An important functioning mechanism of biological macromolecules is the transition between different conformed states due to thermal fluctuation. In the present paper, a biological macromolecule is modeled as two stran...An important functioning mechanism of biological macromolecules is the transition between different conformed states due to thermal fluctuation. In the present paper, a biological macromolecule is modeled as two strands with side chains facing each other, and its stochastic dynamics including the statistics of stationary motion and the statistics of conformational transition is studied by using the stochastic averaging method for quasi Hamikonian systems. The theoretical results are confirmed with the results from Monte Carlo simulation.展开更多
Photoaffinity cross-linking is a fast developing technology for biomolecular interactions,including receptor-ligand binding.The chemical mechanisms of the most commonly used photoactivatable probes and their respectiv...Photoaffinity cross-linking is a fast developing technology for biomolecular interactions,including receptor-ligand binding.The chemical mechanisms of the most commonly used photoactivatable probes and their respective photochemistry are summarized.This review focuses on the expanding utilities of this technology as a result of recent advances in the(i)identification of receptor contact sites,(ii)monitoring ligand-induced receptor conformational changes,(iii)identification of global binding surfaces,(iv)binding mode analysis using bifunctional photo-probes,(v)application of biosynthetic photo-probes,and(vi)examples of novel target discovery using this technology.Limitations and future potential of this approach are also discussed.展开更多
Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the...Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarders and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic im- provements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of func- tional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carders for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imag- ing probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nano- medicine approaches to clinical applications are discussed.展开更多
The Diels–Alder(D–A)reaction is one of the most powerful reactions in organic synthesis.The intermolecular D–A reaction attracts much less attentions than its intramolecular counterpart in natural product synthesis...The Diels–Alder(D–A)reaction is one of the most powerful reactions in organic synthesis.The intermolecular D–A reaction attracts much less attentions than its intramolecular counterpart in natural product synthesis,possibly due to the issues of reactivity and selectivity.In the past decade,the intermolecular D–A reaction has been increasingly utilized in the total synthesis of structurally complex natural products.In this article,we present a few examples for the elegant applications of the intermolecular D–A reaction that are inspired by biosynthetic hypotheses of the target natural products.These examples demonstrate that D–A reaction is not only useful for preparing building blocks but also powerful for coupling structurally complicated and sterically demanding segments in a highly chemo-and stereo-controlled fashion,which may inspire further developments of intermolecular D–A reaction from both strategy and methodology perspectives.展开更多
基金Project supported by the National Natural Science Foundation of China (No.10332030)the Specialized Research Fund for the Doc- toral Program of Higher Education of China (No.20060335125)the National Science Foundation for Post-doctoral Scientists of China (No.20060390338)
文摘An important functioning mechanism of biological macromolecules is the transition between different conformed states due to thermal fluctuation. In the present paper, a biological macromolecule is modeled as two strands with side chains facing each other, and its stochastic dynamics including the statistics of stationary motion and the statistics of conformational transition is studied by using the stochastic averaging method for quasi Hamikonian systems. The theoretical results are confirmed with the results from Monte Carlo simulation.
文摘Photoaffinity cross-linking is a fast developing technology for biomolecular interactions,including receptor-ligand binding.The chemical mechanisms of the most commonly used photoactivatable probes and their respective photochemistry are summarized.This review focuses on the expanding utilities of this technology as a result of recent advances in the(i)identification of receptor contact sites,(ii)monitoring ligand-induced receptor conformational changes,(iii)identification of global binding surfaces,(iv)binding mode analysis using bifunctional photo-probes,(v)application of biosynthetic photo-probes,and(vi)examples of novel target discovery using this technology.Limitations and future potential of this approach are also discussed.
基金supported by the National Heart Lung and Blood Institute of the National Institutes of Health(NIH) as a Program of Excellence in Nanotechnology Award(Grant No.HHSN268201000043C to Bao Gang)an NIH Nanomedicine Development Center Award(Grant No.PN2 EY018244 to Bao Gang)
文摘Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarders and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic im- provements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of func- tional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carders for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imag- ing probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nano- medicine approaches to clinical applications are discussed.
基金financially supported by the Ministry of Science&Technology(2013CB836900)the National Natural Science Foundation of China(21290180,21172235,and 21222202)the Chinese Academy of Sciences
文摘The Diels–Alder(D–A)reaction is one of the most powerful reactions in organic synthesis.The intermolecular D–A reaction attracts much less attentions than its intramolecular counterpart in natural product synthesis,possibly due to the issues of reactivity and selectivity.In the past decade,the intermolecular D–A reaction has been increasingly utilized in the total synthesis of structurally complex natural products.In this article,we present a few examples for the elegant applications of the intermolecular D–A reaction that are inspired by biosynthetic hypotheses of the target natural products.These examples demonstrate that D–A reaction is not only useful for preparing building blocks but also powerful for coupling structurally complicated and sterically demanding segments in a highly chemo-and stereo-controlled fashion,which may inspire further developments of intermolecular D–A reaction from both strategy and methodology perspectives.