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1、文献汇报,2015/12/2,什么是文献汇报,文献汇报是指汇报人对一篇或多篇文献进行深入阅读研究后，对文献研究背景，研究目的，研究方法、研究手段和研究结果以及对汇报人有何启示等方面以书面形式进行的报告。作者为什么要进行研究？怎么样研究？研究结果如何？对汇报人的启发？新课题的启示？对自己工作的指导意义？,为什么要进行文献汇报,汇报人学习和掌握本学科前沿进展，避免“闭门造车以牛人大家的工作为参照，学习研究思路，Idea对自己工作水平的判断组内其它成员了解相关领域的知识，拓宽视野 提高个人写文章的能力，制作PPT的能力和讲演能力督促学习,怎样进行文献汇报,选择文献阅读目标文献及重要参考文献研究文献文
2、献汇报组内讨论（非文献本身）,文献汇报的结构,文献简介 （发表时间，杂志，作者，作者研究领域）文献结构文献思路和文献内容有何启发,如何选择文献,课题相关层次深，影响力强（IF）内容新颖经典文献，最新文献，仪器方法，科普宣传，综述文献,如何查找文献,一般搜索引擎 （Google, Bing, Baidu等）文献搜索引擎 （Pubmed, Web of science， 中国知网，维普等）网络数据库 （Nature，Science, Springer, Elsevier, Wiley, ACS， RSC等）大连理工大学图书馆 ：各学科网络数据库，国内外硕博论文数据库国内论坛：小木虫，丁香园，化学吧
3、等选择和自己领域相关的几个杂志，定期阅读更新的文章,如何查找文献,如何阅读文献,略读概读详读精读,文献结构,背景实验方法实验结果讨论和结论参考文献附加数据,选择文献,文献简介,1. 题目： Organometallic palladium reagents for cysteine bioconjugation 2. 杂志：Nature （IF 41.456）3. 文章类型：Letter （Aticles, News and views）4. 作者：Ekaterina V. Vinogradova1*, Chi Zhang1*, Alexander M. Spokoyny, Bradley L
4、. Pentelute1 & Stephen L. Buchwald15. 作者研究领域：Organic methodology (Buchwald-Hartwig reaction),文献背景(大背景和小背景),大背景（研究意义和研究难点）：Post-translational modifications greatly expand the function of proteins5.Chemists aim to mimic the success of such natural transformations through the development of chemo- and
5、regioselective reactions of proteins. The diversity of potentially reactive functional groupspresent in biomolecules (for example, amides, acids, alcohols, amines)combined with the requirement for fast kinetics and mild reactionconditions (for example, aqueous solvent, pH 68，temperature T,37) make c
6、hallenging the development of new techniques to functionalize proteins.,小背景（同行研究水平）：Nevertheless, methods have emerged for bioconjugation with natural and unnatural amino acids in protein molecules6,7.Cysteine is a key residue for the chemical modification of proteins owing to the unique reactivity
7、of the thiol functional group and the low abundance of cysteine residues in naturally occurring proteins8,9. Michael addition to maleimides and SN2 reaction with alkyl halides are commonly used for cysteine modification. The resulting conjugates tend to decompose in the presence of external bases or
8、 thiol nucleophiles10, which prompted the recent development of advanced cysteine bioconjugations for the improved stability of conjugates.The ability to achieve high levels of chemo- and regioselectivity through the judicious choice of metal and ligand design suggest that metal-mediated processes c
9、ould be very attractive for the development of new bioconjugations. Existing metal-based transformations often rely on the use of functional handles12 or unnatural amino acids, such as 4-iodophenylalanine and aldehyde- or alkyne-containing amino acids3,4,13, and require high concentrations (mM) of d
10、erivatizing agents, which can cause off-target reactivity or purification problems.,文献背景(大背景和小背景),We considered that palladium complexes resulting from the oxidative addition of aryl halides or trifluoromethanesulfonates14 could be used for the transfer of aryl groups to cysteine residues in protein
11、s (Fig. 1a). (For existing transition-metal-catalysed CS bond-forming reactions, see ref. 15.) The efficiency and selectivity of the proposed reaction with the highly active palladium species may be hampered by the presence of a variety of functional groups within complex biomolecules. Furthermore,
12、the presence of free thiols has been previously shown to inhibit palladium-catalysed cross-coupling reactions on peptides16, while Pd(II)-complexes have also been shown to exhibit protease-like behaviour with certain peptides17. However, we envisioned that the careful choice of ligand would provide
13、stable, yet highly reactive reagents for the desired transformations (Fig. 1b),while the interaction between the soft nucleophile cysteine thiol and the aryl palladium(II) species would guide its selectivity.,文献背景(How ideas come),文献背景（新方法、技术或成果的引出）,We began our study with a palladiumtolyl complex (1
14、AOTf; Fig. 1c) using 2-dicyclohexylphosphino-29,69-diisopropoxybiphenyl (RuPhos) as the ligand and trifluoromethanesulfonate as the counterion. A model peptide (P1; Fig. 1c) was used for the optimization of the reaction conditions and for the exploration of the substrate scope. Full conversion of th
15、e starting peptide to the corresponding aryl product was observed in less than 5 min at low micromolar concentrations of reagents (Fig. 1c). Further, the reaction was selective for cysteine. No reaction was observed using a control peptide with cysteine mutated to serine (Supplementary Information),
16、 in contrast to the palladiummediated protein allylation, which is selective for tyrosine (O-allylation) over lysine and cysteine (N- and S-allylation). (The new arylpalladium reagents are less electrophilic than the allylpalladium species used in ref. 18, which tunes their selectivity towards cyste
17、ine residues while making them completely unreactive towards alcoholbased species like tyrosine.) These results highlight the importance of choosing the right ligand, which facilitates CS reductive elimination and, together with the overall electrophilicity of the palladium centre, tunes the selecti
18、vity of the transformation.,实验结果与讨论 （条件筛选）,实验结果与讨论（条件筛选）,底物扩展1（Substrate scope）,底物扩展2（Substrate scope）,底物扩展3（Substrate scope）,实验结论,We note that the ease of preparation, storage and use of the present palladium reagents make them particularly attractive for routine application in chemistry, biology,
19、medicine and materials science. Further evolution of the metals and ligands employed will probably provide an extended set of organometallic bioconjugation reagents with altered selectivity and efficiency, allowing for functionalization of other amino acid residues.,Supporting Information（具体实验方法和技术）,文献汇报时应整合文章和SI，综合进行汇报,启示与组内讨论,1. 视野 将有机化学方法学应用于大分子的修饰改造2. 应用 （1）抗体和药物分子的复合物 （2）靶向药物的设计,谢谢大家！,
