大学精品课件：专业英语Section II.ppt

1、Section I Practice Reading Skills by Reading the Materials Related to Pharmaceutical ScienceSome knowledge of drug names can help in understanding drug product labels.Every drug has at least three names:a chemical name,a generic(nonproprietary or official)name,and a trade(proprietary or brand)name.b

2、rand:A trademark or distinctive name identifying a product or a manufacturer.商标：标志一种产品或制造商标：标志一种产品或制造商的商标或特有名称；商的商标或特有名称；A product line so identified;品品牌：如此标识的产品系列：牌：如此标识的产品系列：Drug NameThe chemical name describes the atomic or molecular structure of the drug.This name is usually too complex and cumb

3、ersome（麻烦的，讨（麻烦的，讨厌的）厌的）for general use.So an official body assigns a generic name to a drug.The generic names for drugs of a particular type(class)usually have the same ending.For example,the names of all beta-blockers,which are used to treat such disorders as high blood pressure,end in lol.The tra

4、de name is chosen by the pharmaceutical company that manufactures or distributes the drug.Patented drugs are usually sold under a trade name.Generic versions of trade-name drugsmanufactured after expiration of the pharmaceutical companys patentmay be sold under the generic name(for example,ibuprofen

5、布洛芬布洛芬)or under the manufacturers own trade name(for example,Advil).Drug DesignDrug design is the approach of finding drugs by design,based on their biological targets.Typically a drug target is a key molecule involved in a particular metabolic(代谢）代谢）or signalling pathway（信号通路）（信号通路）that is specific

6、 to a disease condition or pathology（病理）（病理）,or to the infectivity or survival of a microbial pathogen（病原体）（病原体）.Some approaches attempt to stop the functioning of the pathway in the diseased state by causing a key molecule to stop functioning.Drugs may be designed that bind to the active region and

7、 inhibit this key molecule.However these drugs would also have to be designed in such a way as not to affect any other important molecules that may be similar in appearance to the key molecules.Sequence homologies（序列同源）（序列同源）are often used to identify such risks.Other approaches may be to enhance th

8、e normal pathway by promoting specific molecules in the normal pathways that may have been affected in the diseased state.The structure of the drug molecule that can specifically interact with the biomolecules can be modeled using computational tools.These tools can allow a drug molecule to be const

9、ructed within the biomolecule using knowledge of its structure and the nature of its active site.Construction of the drug molecule can be made inside out or outside in depending on whether the core or the R-groups are chosen first.However many of these approaches are plagued by the practical problem

10、s of chemical synthesis.Newer approaches have also suggested the use of drug molecules that are large and protein aceous（似蛋白质的，蛋白质的）似蛋白质的，蛋白质的）in nature rather than as small molecules.There have also been suggestions to make these using mRNA.Gene silencing（基因沉默（基因沉默）may also have therapeutically app

11、lications.Unlike the historical method of drug discovery,by trial-and-error（反复试验）（反复试验）testing of chemical substances on animals,and matching the apparent effects to treatments,rational drug design begins with a knowledge of specific chemical responses in the body or target organism,and tailoring co

12、mbinations of these to fit a treatment profile.Due to the complexity of the drug design process two terms of interest are still serendipity（意外发现的）（意外发现的）and bounded rationality.Those challenges are caused by the large chemical space describing potential new drugs without side-effects.A particular ex

13、ample of rational drug design involves the use of three-dimensional information about biomolecules obtained from such techniques as x-ray crystallography and NMR spectroscopy.This approach to drug discovery is sometimes referred to as structure-based drug design.The first unequivocal（明确的）（明确的）exampl

14、e of the application of structure-based drug design leading to an approved drug is the carbonic anhydrase inhibitor（碳酸酐酶抑制剂）碳酸酐酶抑制剂）dorzolamide（多佐胺）多佐胺）which was approved in 1995.Another important case study in rational drug design is imatinib(伊马替尼伊马替尼),a tyrosine kinase(酪氨酪氨酸激酶酸激酶)inhibitor designe

15、d specifically for the bcr-abl fusion protein(融合蛋白融合蛋白)that is characteristic for Philadelphia chromosome-positive leukemias(费费城染色体阳性白血病城染色体阳性白血病)(chronic myelogenous(骨髓性骨髓性的的)leukemia(白血病白血病)and occasionally acute lymphocytic(淋巴细胞的淋巴细胞的)leukemia).Imatinib is substantially different from previous dr

16、ugs for cancer,as most agents of chemotherapy simply target rapidly dividing cells,not differentiating between cancer cells and other tissues.The activity of a drug at its binding site is one part of the design.Another to take into account is the molecules druglikeness(类药性类药性),which summarizes the n

17、ecessary physical properties for effective absorption.One way of estimating druglikeness is Lipinskis Rule of Five(类药类药5规则规则).The first step of drug discovery involves the identification of new active compounds,often called“hits”,which are typically found by screening many compounds for the desired

18、biological properties.These hits can come from natural sources,such as plants,animals,or fungi（真菌）（真菌）.More often,the hits can come from synthetic sources,such as historical compound collections and combinatorial chemistry（组合化学）（组合化学）.fungi：真菌类：真菌类(包括霉菌包括霉菌,食用伞菌食用伞菌,酵母菌等酵母菌等),似真似真菌的菌的,由真菌引起的由真菌引起的Dr

19、ug DiscoveryRecent developments in robotics and miniaturization have incredibly accelerated and automated the screening process.Typically,a company will assay over 100,000 individual compounds using a method called high-throughput screening(HTS),before moving to the optimization step.The second step

20、 of drug discovery involves the synthetic modification of the hits in order to improve the biological properties of the compound pharmacophore(药效团药效团).The quantitative structure-activity relationship(QSAR)of the pharmacophore play an important part in finding lead compounds(先导化合物先导化合物),which exhibit

21、 the most potency(力量力量),most selectivity,best pharmacokinetics and least toxicity.QSAR involves mainly physical chemistry and molecular docking tools(CoMFA,CoMSIA and many others methods),that leads to tabulated data and first and second order equations.There are many theories,being the most relevan

22、t Hanschs analysis that involves Hammett electronic parameters,Esteric parameters and logP parameters.The final step involves the rendering（使成为（使成为：使：使成为；制成）成为；制成）the lead compounds suitable for use in clinical trials.This involves the optimization of the synthetic route for bulk production,and the

23、preparation of a suitable drug formulation.Title of scientific papersThe basic requirement for title(ABC)AccuracyBrevityClarityAbstract of scientific papersWhat the objectives of the study were;How the study was done;What results were obtained;The significance of the results.ExamplesIon Channels as

24、Therapeutic Targets:A Drug Discovery PerspectiveIon channels are membrane proteins expressed in almost all living cells.The sequencing of the human genome has identified more than 400 putative ion channels,but only a fraction of these have been cloned and functionally tested.The widespread tissue di

25、stribution of ion channels,coupled with the plethora of physiological consequences of their opening and closing,makes ion-channel-targeted drug discovery highly compelling.However,despite some important drugs in clinical use today,as a class,ion channels remain underexploited in drug discovery and m

26、any existing drugs are poorly selective with significanttoxicities or suboptimal efficacy.This Perspective seeks to review the ion channel family,its structural and functional features,and the diseases that are known to be modulated by members of the family.In particular,we will explore the structur

27、e and properties of known ligands and consider the future prospects for drug discovery in this challenging but high potential area.Regulation of-Secretase Activity in Alzheimers DiseaseThe-secretase complex is an intramembrane aspartyl（天冬氨酰(基)protease that cleaves its substrates along their transmem

28、brane regions.Sequential proteolytic(蛋白水解的)processing of amyloid precursor protein by-and-secretase produces amyloid-peptides,which are the major components of amyloid plaques in the brains of Alzheimers disease patients.The-secretase complex is therefore believed to be critical in the pathogenesis（

29、发病机理）of Alzheimers disease.Here we review the range offactors found to affect the nature and degree of-secretase complex activity;these include-secretase complex assembly and activation,the integral regulatory subunit CD147,transient or weak binding partners,the levels of cholesterol and sphingolipi

30、ds（鞘脂类）in cell membranes,and inflammatory cytokines（细胞活素类）.Integrated knowledge of the molecular mechanisms supporting the actions of these factors is expected to lead to a comprehensive understanding of the functional regulation of the-secretase complex,and this,in turn,should facilitate the develo

31、pment of novel therapeutic strategies for the treatment of Alzheimers disease.Structural Insight into the Transglycosylation Step of Bacterial Cell-Wall Biosynthesis Peptidoglycan glycosyltransferases(GTs)catalyze the polymerization step of cell-wall biosynthesis,are membrane-bound,and are highly co

32、nserved across all bacteria.Long considered the holy grail of antibiotic research,they represent an essential and easily accessible drug target for antibiotic-resistant bacteria,including methicillin-resistant Staphylococcus aureus.We have determined the 2.8 angstrom structure of a bifunctional cell

33、-wall cross-linking enzyme,including its transpeptidase（转肽酶）and GT domains,both unliganded and complexed with the substrate analog moenomycin.The peptidoglycan GTs adopt a fold distinct from those of other GT classes.The structures give insight into critical features of the catalytic mechanism and key interactions required for enzyme inhibition.