演講MP3+雙語(yǔ)文稿:一種用微型蛋白質(zhì)定制而成的新型藥物

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聽力課堂TED音頻欄目主要包括TED演講的音頻MP3及中英雙語(yǔ)文稿，供各位英語(yǔ)愛好者學(xué)習(xí)使用。本文主要內(nèi)容為演講MP3+雙語(yǔ)文稿:一種用微型蛋白質(zhì)定制而成的新型藥物，希望你會(huì)喜歡！

【演講者及介紹】Christopher Bahi

TED的研究員Christopher Bahl使用計(jì)算蛋白質(zhì)設(shè)計(jì)——在計(jì)算機(jī)的幫助下建立自然界中從未見過的蛋白質(zhì)——來開發(fā)用于對(duì)抗傳染病的新藥。

【演講主題】一種用微型蛋白質(zhì)定制而成的新型藥物

A new type of medicine, custom-made with tiny proteins

【中英文字幕】

翻譯者 Archi Xiao 校對(duì)者Wanting Zhong

00:19

I'm a protein designer. And I'd like to discuss a new type of medicine. It's made from a molecule called a constrained peptide.

我是一名蛋白質(zhì)設(shè)計(jì)師。 我想跟大家談?wù)勔环N新型藥物。 它是由一種名為限制性肽的分子構(gòu)成的。

00:30

There are only a few constrained peptide drugs available today, but there are a lot that will hit the market in the coming decade. 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.

現(xiàn)在市面上只有少量限制性肽藥物， 但是在未來的十年里，有許多的藥物投放市場(chǎng)。 我們來看看這些新藥是由什么做的， 她們是如何不同的， 是什么導(dǎo)致了這股新的、令人興奮的藥物浪潮的到來。

00:44

Constrained peptides are very small proteins. They've got extra chemical bonds that constrain the shape of the molecule, and this makes them incredibly stable as well as highly potent. They're naturally occurring, our bodies actually produce a few of these that help us to combat bacterial, fungal and viral infections. And animals like snakes and scorpions use constrained peptides in their venom.

限制性肽是一種很小的蛋白質(zhì)。 它們有額外的化學(xué)鍵限制分子的形狀，這使得它們既穩(wěn)定又高效。 它們是自然發(fā)生的， 我們的身體實(shí)際上產(chǎn)生了一些物質(zhì)能幫助我們對(duì)抗細(xì)菌、真菌和病毒感染。像蛇和蝎子這樣的動(dòng)物， 它們的毒液里也含有限制性肽。

01:06

Drugs that are made of protein are called biologic drugs. So this includes constrained peptides, as well as medicines like insulin or antibody drugs like Humira or Enbrel. And in general, biologics are great, because they avoid several ways that drugs can cause side effects.

由蛋白質(zhì)制成的藥物被稱為生物藥物。 其中包括限制性肽，還有胰島素之類的藥物，或者像 Humira 或 Enbrel這樣的抗體藥物。 總的來說，生物藥品很好， 因?yàn)樗鼈兡鼙苊饬怂幬镆l(fā)的副作用的幾種方式。

01:25

First, protein. It's a totally natural, nontoxic material in our bodies. Our cells produce tens of thousands of different proteins, and basically, all of our food has protein in it. And second, sometimes drugs interact with molecules in your body that you don't want them to. Compared to small molecule drugs, and by this I mean regular drugs, like aspirin, biologics are quite large.

首先是蛋白質(zhì)。 它是我們體內(nèi)純天然、 無毒性的物質(zhì)。 我們的細(xì)胞能合成成千上萬種不同的蛋白質(zhì)， 我們所有的食物基本都含有蛋白質(zhì)。 第二，有時(shí)候藥物會(huì)跟你體內(nèi)的分子相互反應(yīng)， 而你不希望它們發(fā)生作用。 與小分子藥物相比，這里我指的是普通藥物，比如阿司匹林，生物制劑相當(dāng)大。

01:47

Molecules interact when they adopt shapes that fit together perfectly. Much like a lock and key. Well, a larger key has more grooves, so it's more likely to fit into a single lock. But most biologics also have a flaw. They're fragile. So they're usually administered by injection, because our stomach acid would destroy the medicine if we tried to swallow it.

當(dāng)分子采用完美地結(jié)合在一起的形狀時(shí)， 它們便會(huì)相互作用。 就像一把鎖和鑰匙。 更大的鑰匙有更多的溝槽，所以它更有可能裝進(jìn)一把鎖里。 但大多數(shù)生物藥品都有一個(gè)缺陷。它們很脆弱， 所以通常是通過注射給藥， 因?yàn)槿绻?dāng)我們?cè)噲D口服的時(shí)候， 胃酸可能會(huì)讓藥物失效。

02:08

Constrained peptides are the opposite. They're really durable, like regular drugs. So it's possible to administer them using pills, inhalers, ointments. This is what makes constrained peptides so desirable for drug development. They combine some of the best features of small-molecule and biologic drugs into one. But unfortunately, it's incredibly difficult to reengineer the constrained peptides that we find in nature to become new drugs.

限制性肽則相反。 它們跟常規(guī)藥一樣很耐久。 所以可以用藥丸、氣霧劑、藥膏給他們服用。 這正是限制性肽在藥物開發(fā)中備受青睞的原因。 它們把小分子藥和生物藥品最好的一些特征合為一體。 但不幸的是，要想重組我們?cè)谧匀唤缰邪l(fā)現(xiàn)的限制性肽， 將其制成新藥非常困難的。

02:34

So this is where I come in. Creating a new drug is a lot like crafting a key to fit a particular lock. We need to get the shape just right. 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. So we needed to figure out how to gain control over their shape.

所以這就是我研究的領(lǐng)域。 創(chuàng)造一種新型藥物就好像制作一把鑰匙來裝上一個(gè)特別的鎖。 我們得把形狀弄得恰到好處。 但是如果我們過多改變 限制性肽的形狀， 那些額外的化學(xué)鍵便無法形成，整個(gè)分子結(jié)構(gòu)也會(huì)隨之瓦解。 因此我們得需要弄清楚如何控制好它們的形狀。

02:54

I was part of a collaborative scientific effort that spanned a dozen institutions across three continents that came together and solved this problem. We took a radically different approach from previous efforts. Instead of making changes to the constrained peptides that we find in nature, we figured out how to build new ones totally from scratch. To help us do this, we developed freely available open-source peptide-design software that anyone can use to do this, too.

我參與了一項(xiàng)跨越十幾個(gè)結(jié)構(gòu)、跨越三大洲、共同解決這一問題是科學(xué)合作。我們采取了與以前的努力截然不同的做法。 我們并沒有選擇改變天然的限制性肽， 而是發(fā)現(xiàn)了如何從頭開始制造全新的限制性肽。 為了達(dá)到目標(biāo)， 我們開發(fā)了免費(fèi)的開放源碼鈦設(shè)計(jì)軟件，任何人都可以使用。

03:19

To test our method out, we generated a series of constrained peptides that have a wide variety of different shapes. Many of these had never been seen in nature before. Then we went into the laboratory and produced these peptides. Next, we determined their molecular structures, using experiments. 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. Three years ago, this couldn't be done. But today, we have the ability to create designer peptides with shapes that are custom-tailored for drug development.

為了測(cè)試我們的方法， 我們生成了一系列具有多種不同形狀的限制性肽。 其中很多從未在自然界中出現(xiàn)過。 接著我們到實(shí)驗(yàn)室制造這些限制性肽。 接下來，我們用實(shí)驗(yàn)確定了它們的分子結(jié)構(gòu)。 當(dāng)我們將自己所設(shè)計(jì)的模型跟真實(shí)的分子結(jié)構(gòu)進(jìn)行比較時(shí)， 我們發(fā)現(xiàn)該軟件可以精確地定位單個(gè)原子，其精確度處于可測(cè)量的極限。 這在三年前是不可能辦到的。 但是今天，我們擁有制造設(shè)計(jì)肽的能力， 能為藥物開發(fā)定制 （限制肽的）形狀。

03:54

So where is this technology taking us? Well, recently, my colleagues and I designed constrained peptides that neutralize influenza virus, protect against botulism poisoning and block cancer cells from growing. Some of these new drugs have been tested in preclinical trials with laboratory animals. And so far, they're all safe and highly effective.

那么這項(xiàng)技術(shù)將 引導(dǎo)我們前往何方？ 最近， 我和同事們?cè)O(shè)計(jì)出了抑制肽，可以中和流感病毒、 防止肉毒桿菌中毒、 阻止癌細(xì)胞增長(zhǎng)。 其中一些新型藥物已經(jīng)在實(shí)驗(yàn)室里用動(dòng)物進(jìn)行了臨床前試驗(yàn)。 目前來看，它們都很安全， 且非常高效。

04:18

Constrained peptide design is a cutting-edge technology, and the drug development pipeline is slow and cautious. So we're still three to five years out from human trials. But during that time, more constrained peptide drugs are going to be entering the drug development pipeline. And ultimately, I believe that designed peptide drugs are going to enable us all to break free from the constraints of our diseases.

限制性肽設(shè)計(jì)是一項(xiàng)前沿技術(shù)，同時(shí)藥物開發(fā)的進(jìn)程漫長(zhǎng)而謹(jǐn)慎。 因此我們還需三到五年才能開始人體試驗(yàn)。 但與此同時(shí)，有更多的限制性肽藥物將進(jìn)入藥物開發(fā)進(jìn)程中。 最終，我相信限制性肽藥物將讓我們從疾病的枷鎖中得到徹底的解放。

04:40

Thank you.

謝謝大家。

04:41

(Applause)

（掌聲）