TED演讲-一种用微型蛋白质定制而成的新型药物ChristopheBahl(中英文参考学习)48

1、【演讲者及介绍】Christopher BahiTED的研究员Christopher Bahl使用计算蛋白质设计在计算机的帮助下建立自然界中从未见过的蛋白质来开发用于对抗传染病的新药。【演讲主题】一种用微型蛋白质定制而成的新型药物 A new type of medicine, custom-made with tiny proteins【中英文字幕】翻译者 Archi Xiao 校对者Wanting Zhong00:19Im a protein designer. And Id like to discuss a new type of medicine. Its made from a molecule called a constrained peptide. 我是一名蛋白质设计师。 我想跟大家谈谈一种新型药物。 它是由一种名为限制性肽的分子构成的。 00:30There are only a few constrained peptide drugs available today, but there are a lot that will hit the market in

2、 the coming decade. Lets explore what these new medicines are made of, how theyre different and whats causing this incoming tidal wave of new and exciting medicines. 现在市面上只有少量限制性肽药物， 但是在未来的十年里，有许多的药物投放市场。 我们来看看这些新药是由什么做的， 她们是如何不同的， 是什么导致了这股新的、令人兴奋的药物浪潮的到来。 00:44Constrained peptides are very small proteins. Theyve got extra chemical bonds that constrain the shape of the molecule, and this makes them incredibly stable as well as highly potent. Theyre naturally occurring, our bodies actually produc

3、e 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. 限制性肽是一种很小的蛋白质。 它们有额外的化学键限制分子的形状，这使得它们既稳定又高效。 它们是自然发生的， 我们的身体实际上产生了一些物质能帮助我们对抗细菌、真菌和病毒感染。像蛇和蝎子这样的动物， 它们的毒液里也含有限制性肽。 01:06Drugs 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

4、 avoid several ways that drugs can cause side effects. 由蛋白质制成的药物被称为生物药物。 其中包括限制性肽，还有胰岛素之类的药物，或者像 Humira 或 Enbrel这样的抗体药物。 总的来说，生物药品很好， 因为它们能避免了药物引发的副作用的几种方式。 01:25First, protein. Its 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 dont want them to. Compared to small molecule drugs, and by this I mean regular dru

5、gs, like aspirin, biologics are quite large. 首先是蛋白质。 它是我们体内纯天然、 无毒性的物质。 我们的细胞能合成成千上万种不同的蛋白质， 我们所有的食物基本都含有蛋白质。 第二，有时候药物会跟你体内的分子相互反应， 而你不希望它们发生作用。 与小分子药物相比，这里我指的是普通药物，比如阿司匹林，生物制剂相当大。 01:47Molecules interact when they adopt shapes that fit together perfectly. Much like a lock and key. Well, a larger key has more grooves, so its more likely to fit into a single lock. But most biologics also have a flaw. Theyre fragile. So theyre usually administered by injection, because our stomach acid would destr

6、oy the medicine if we tried to swallow it. 当分子采用完美地结合在一起的形状时， 它们便会相互作用。 就像一把锁和钥匙。 更大的钥匙有更多的沟槽，所以它更有可能装进一把锁里。 但大多数生物药品都有一个缺陷。它们很脆弱， 所以通常是通过注射给药， 因为如果当我们试图口服的时候， 胃酸可能会让药物失效。 02:08Constrained peptides are the opposite. Theyre really durable, like regular drugs. So its 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 unfortu

7、nately, its incredibly difficult to reengineer the constrained peptides that we find in nature to become new drugs. 限制性肽则相反。 它们跟常规药一样很耐久。 所以可以用药丸、气雾剂、药膏给他们服用。 这正是限制性肽在药物开发中备受青睐的原因。 它们把小分子药和生物药品最好的一些特征合为一体。 但不幸的是，要想重组我们在自然界中发现的限制性肽， 将其制成新药非常困难的。 02:34So 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

8、 and the whole molecule falls apart. So we needed to figure out how to gain control over their shape. 所以这就是我研究的领域。 创造一种新型药物就好像制作一把钥匙来装上一个特别的锁。 我们得把形状弄得恰到好处。 但是如果我们过多改变 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。 因此我们得需要弄清楚如何控制好它们的形状。 02:54I 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 th

9、at 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. 我参与了一项跨越十几个结构、跨越三大洲、共同解决这一问题是科学合作。我们采取了与以前的努力截然不同的做法。 我们并没有选择改变天然的限制性肽， 而是发现了如何从头开始制造全新的限制性肽。 为了达到目标， 我们开发了免费的开放源码钛设计软件，任何人都可以使用。 03:19To 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 thats at the limit of whats possible to measure. Three years ago, this couldnt be done. But today, we have the ability to cr

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