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ChristopherBahl_2019U-_用小分子蛋白质定制的新型药物_-
I'm a protein designer. 我是一名蛋白质设计师。
protein:n.蛋白质;
And I'd like to discuss a new type of medicine. 我想跟大家谈谈一种新型药物。
It's made from a molecule called a constrained peptide . 它是由一种名为限制性肽 的分子构成的。
molecule:n.[化学]分子;微小颗粒,微粒; constrained:adj.不自然的; v.约束; (constrain的过去分词和过去式) peptide:n.[生化]缩氨酸;
There are only a few constrained peptide drugs available today, but there are a lot that will hit the market in the coming decade. 现在市面上只有少量 限制性肽药物, 但是在接下来的十年里 将会有更多这样的药物面世。
Let's explore what these new medicines are made of, how they're different and what's causing this incoming tidal wave of new and exciting medicines. 我们来看看这些新药 是由什么构成的, 有什么不同, 以及是什么正掀起一场 崭新又振奋人心的药物浪潮。
explore:v.探索:探测:探险: incoming:n.进来;收入;adj.新当选的;新任的; tidal:adj.潮汐的;潮的,有关潮水的;定时涨落的;
Constrained peptides are very small proteins . 限制性肽是非常小的蛋白质分子。
peptides:n.多肽类;[生化]缩氨酸; proteins:n.[生化]蛋白质(protein复数);
They've got extra chemical bonds that constrain the shape of the molecule, and this makes them incredibly stable as well as highly potent . 它们拥有额外的化学键 来约束分子结构, 因此它们异常稳定, 效力强大。
extra:adj.额外的:n.额外的事物:adv.额外:另外: chemical:n.化学制品,化学药品;adj.化学的; incredibly:adv.难以置信地;非常地; stable:n.马厩;牛棚;adj.稳定的;牢固的;坚定的;vi.被关在马厩;赶入马房; as well as:也;和…一样;不但…而且; highly:adv.高度地;非常;非常赞许地; potent:adj.有效的;强有力的,有权势的;有说服力的;
They're naturally occurring , our bodies actually produce a few of these that help us to combat bacterial , fungal and viral infections . 它们是天然生成的分子, 人体自身就会产生一些限制肽 来帮助我们对抗细菌、 真菌和病毒感染。
naturally:adv.自然地;自然而然地;轻而易举;天生地;大方地; occurring:n.事件;事故;事变; combat:v.战斗;防止;减轻;与…搏斗;n.战斗;搏斗;打仗; bacterial:adj.[微]细菌的; fungal:adj.真菌的(等于fungous); viral:adj.滤过性毒菌引起的;滤过性毒菌的; infections:n.传染病;口腔病害(infection复数形式);
And animals like snakes and scorpions use constrained peptides in their venom . 像蛇和蝎子一类的动物, 它们的毒液里也含有限制性肽。
scorpions:n.蝎子;蝎形弩(scorpion的复数形式); venom:n.毒液;恶意;vt.使有毒;放毒;
Drugs that are made of protein are called biologic drugs. 由蛋白质制成的药物 被称为生物药品。
biologic:adj.生物的;生物学的;
So this includes constrained peptides, as well as medicines like insulin or antibody drugs like Humira or Enbrel. 其中包括限制性肽, 还有胰岛素, 或者抗体药物,如修美乐或恩博 【注:自身免疫疾病用药】。
insulin:n.[生化][药]胰岛素; antibody:n.[免疫]抗体;
And in general , biologics are great, because they avoid several ways that drugs can cause side effects. 一般来说,生物药品很好, 因为它们能避免若干 药物引发的副作用。
in general:总之,通常;一般而言; biologics:n.生物制品;生物制剂;生物产品;
First, protein. 首先,我们来说说蛋白质。
It's a totally natural, nontoxic material in our bodies. 它是我们体内纯天然、 无毒性的物质。
nontoxic:adj.无毒的;
Our cells produce tens of thousands of different proteins, and basically , all of our food has protein in it. 我们的细胞能合成 成千上万种不同的蛋白质, 我们的食物基本都 含有蛋白质。
basically:adv.主要地,基本上;
And second, sometimes drugs interact with molecules in your body that you don't want them to. 第二,有时候药物会跟 你体内的分子反应, 这是你不希望发生的。
interact:v.互相影响;互相作用;n.幕间剧;幕间休息; molecules:n.[化学]分子,微粒;[化学]摩尔(molecule的复数);
Compared to small molecule drugs, and by this I mean regular drugs, like aspirin , biologics are quite large. 相比起小分子药物, 这里我指的是阿司匹林 之类的常规药物, 生物药品分子挺大的。
Compared:adj.比较的,对照的; v.相比; (compare的过去式和过去分词) aspirin:n.阿司匹林(解热镇痛药);
Molecules interact when they adopt shapes that fit together perfectly. 当分子的形状能天衣无缝地契合, 它们便会相互作用。
adopt:v.采取;接受;收养;正式通过;
Much like a lock and key. 就像是锁配钥匙一样。
Well, a larger key has more grooves , so it's more likely to fit into a single lock. 一把较大的钥匙有更多的沟槽, 因此很可能只匹配单个锁。
grooves:n.细槽,[建]凹槽(groove的复数);
But most biologics also have a flaw . 但是多数生物药品 都有一个缺陷。
flaw:n.瑕疵,缺点; v.使生裂缝,使有裂纹; vi.生裂缝;
They're fragile . 它们往往比较脆弱,
fragile:adj.脆的;易碎的;
So they're usually administered by injection , because our stomach acid would destroy the medicine if we tried to swallow it. 因此通常是注射给药, 因为当我们试图口服的时候, 胃酸可能会让药物失效。
administered:v.管理;治理(国家);执行;给予;提供;(administer的过去分词和过去式) injection:n.注射;大量资金的投入;(液体的)注入; swallow:v.吞下;咽下;吞没;相信;n.吞;咽;燕;一次吞咽的量;
Constrained peptides are the opposite. 限制性肽刚好相反。
They're really durable , like regular drugs. 它们跟常规药一样很耐久。
durable:adj.耐用的;耐久的;长期的;长久的;n.耐久品;
So it's possible to administer them using pills , inhalers , ointments . 因此给药方式可以是 药丸、气雾剂、药膏。
pills:n.药丸; v.起球; (pill的第三人称单数和复数) inhalers:n.[临床]吸入器;吸气者;滤气器;小口矮脚酒杯(inhaler的复数); ointments:n.药膏(ointment的复数);[药]油膏;软膏剂;
This is what makes constrained peptides so desirable for drug development. 这正是限制性肽在药物开发中 备受青睐的原因。
desirable:adj.令人满意的;值得要的;n.合意的人或事物;
They combine some of the best features of small-molecule and biologic drugs into one. 它们把小分子药和生物药品 最好的一些特征合为一体。
But unfortunately , it's incredibly difficult to reengineer the constrained peptides that we find in nature to become new drugs. 但不幸的是,要想重组 自然界中的限制性肽, 将其制成新药, 是异常困难的。
unfortunately:adv.不幸地; reengineer:vt.再设计;重新建造;再设法处理;
So this is where I come in. 这就是我的领域了。
Creating a new drug is a lot like crafting a key to fit a particular lock. 创造一种新型药物就好像是 为某把特定的锁 打造匹配的钥匙。
crafting:n.工艺;手工艺;v.精巧地制作;加工制作(craft的ing形式);
We need to get the shape just right. 形状尤为关键。
But if we change the shape of a constrained peptide by too much, those extra chemical bonds are unable to form and the whole molecule falls apart. 但是如果我们过度改变 限制性肽的形状, 那些额外的化学键便无法形成, 整个分子结构也会随之瓦解。
So we needed to figure out how to gain control over their shape. 因此我们得解决 如何控制好它们的形状的问题。
I was part of a collaborative scientific effort that spanned a dozen institutions across three continents that came together and solved this problem. 来自三大洲的十几个机构 组成了一个科研合作小组 来解决这个问题, 我当时是其中的一员。
collaborative:adj.合作的,协作的; scientific:adj.科学的,系统的; spanned:adj.生活期有限的; institutions:n.机构;慈善机构;风俗习惯,制度;(institution的复数) continents:n.[地理]大陆,大洲(continent复数);
We took a radically different approach from previous efforts. 我们采取了与之前的尝试 截然不同的方法。
radically:adv.根本上;彻底地;以激进的方式; approach:n.方法;路径;v.接近;建议;着手处理; previous:adj.以前的;早先的;过早的;adv.在先;在…以前;
Instead of making changes to the constrained peptides that we find in nature, we figured out how to build new ones totally from scratch . 我们并没有选择改变 天然的限制性肽, 而是发现了如何从零开始 制造全新的限制性肽。
from scratch:白手起家;从头做起;
To help us do this, we developed freely available open-source peptide-design software that anyone can use to do this, too. 为了达到目标, 我们开发了免费开源的 限制性肽设计软件, 任何人都可以使用。
open-source:adj.(计算机)开放源代码;
To test our method out, we generated a series of constrained peptides that have a wide variety of different shapes. 为了测试我们的方法, 我们生成了一系列限制性肽, 形状不一、种类繁多。
generated:v.产生;引起;(generate的过去式和过去分词) series:n.系列,连续;[电]串联;级数;丛书; variety:n.多样;种类;杂耍;变化,多样化;
Many of these had never been seen in nature before. 其中很多是自然界 前所未有的。
Then we went into the laboratory and produced these peptides. 接着我们到实验室 制造这些限制性肽。
laboratory:n.实验室,研究室;
Next, we determined their molecular structures , using experiments. 接下来,我们用实验确定了 它们的分子结构。
determined:adj.决定了的:v.决定;(determine的过去分词和过去式) molecular:adj.[化学]分子的;由分子组成的; structures:n.结构; v.建造(structure的第三人称单数形式);
When we compared our designed models with the real molecular structures, we found that our software can position individual atoms with an accuracy that's at the limit of what's possible to measure. 当我们将自己所设计的模型 跟真实的分子结构作对比的时候, 我们发现该软件 能以可测量的最大精度 来设计单个原子的位置。
individual:n.个人;有个性的人;adj.单独的;个别的; atoms:n.[物]原子(atom的复数); accuracy:n.[数]精确度,准确性;
Three years ago, this couldn't be done. 这在三年前是不可能办到的。
But today, we have the ability to create designer peptides with shapes that are custom-tailored for drug development. 但是今天,我们拥有 制造设计肽的能力, 能为药物开发定制 （限制肽的）形状。
custom-tailored:vt.定制;定做;
So where is this technology taking us? 那么这项技术将 引导我们前往何方？
Well, recently , my colleagues and I designed constrained peptides that neutralize influenza virus, protect against botulism poisoning and block cancer cells from growing. 最近, 我和同事们设计出了 能消除流感病毒、 能防止肉毒杆菌中毒、 能抑制癌细胞增长的限制性肽。
recently:adv.最近;新近; colleagues:n.同事;同行(colleague的复数); neutralize:vt.抵销;使…中和;使…无效;使…中立;vi.中和;中立化;变无效; influenza:n.[内科]流行性感冒(简写flu);家畜流行性感冒; protect against:使免受; botulism:n.[内科][毒物]肉毒中毒(食物中毒一种); cancer:n.癌症;恶性肿瘤;
Some of these new drugs have been tested in preclinical trials with laboratory animals. 其中一些新型药物 已经在实验室里用动物 进行了临床前试验。
preclinical:adj.临床前的;现出症状之前的潜伏期的;
And so far, they're all safe and highly effective . 目前来看,它们都很安全, 且非常高效。
effective:adj.有效的,起作用的;实际的,实在的;给人深刻印象;
Constrained peptide design is a cutting-edge technology , and the drug development pipeline is slow and cautious . 限制性肽设计 是一项前沿技术, 同时药物开发的进程 漫长而谨慎。
cutting-edge technology:尖端技术;前沿的技术; cautious:adj.谨慎的;十分小心的;
So we're still three to five years out from human trials. 因此我们还需三到五年 才能开始人体试验。
But during that time, more constrained peptide drugs are going to be entering the drug development pipeline. 但与此同时, 有更多的限制性肽药物 将进入药物开发进程中。
And ultimately , I believe that designed peptide drugs are going to enable us all to break free from the constraints of our diseases . 最终,我相信限制性肽药物 将让我们从疾病的枷锁中 得到彻底的解放。
ultimately:adv.最终;最后;归根结底;终究; enable:v.使能够;使有机会;使成为可能;使可行; constraints:n.[数]约束;限制;约束条件(constraint的复数形式); diseases:n.[医]病(disease的复数);[医]疾病;[植保]病害;疾病种类;
Thank you. 谢谢大家。
(Applause) （掌声）