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。
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.
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。 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。
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.
限制性肽是非常小的蛋白质分子。 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。 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。 像蛇和蝎子一类的动物, 它们的毒液里也含有限制性肽。
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.
由蛋白质制成的药物 被称为生物药品。 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】。 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。
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,我们来说说蛋白质。 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 你体内的分子反应, 这是你不希望发生的。 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。
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.
当分子的形状能天衣无缝地契合, 它们便会相互作用。 就像是锁配钥匙一样。 一把较大的钥匙有更多的沟槽, 因此很可能只匹配单个锁。 但是多数生物药品 都有一个缺陷。 它们往往比较脆弱, 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。
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.
限制性肽刚好相反。 它们跟常规药一样很耐久。 因此给药方式可以是 药丸、气雾剂、药膏。 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 自然界中的限制性肽, 将其制成新药, 是异常困难的。
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.
这就是我的领域了。 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。 形状尤为关键。 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。 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. 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.
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。 我们采取了与之前的尝试 截然不同的方法。 我们并没有选择改变 天然的限制性肽, 而是发现了如何从零开始 制造全新的限制性肽。 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。
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.
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。 其中很多是自然界 前所未有的。 接着我们到实验室 制造这些限制性肽。 接下来,我们用实验确定了 它们的分子结构。 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。 这在三年前是不可能办到的。 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。
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.
那么这项技术将 引导我们前往何方? 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。 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。 目前来看,它们都很安全, 且非常高效。
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.
限制性肽设计 是一项前沿技术, 同时药物开发的进程 漫长而谨慎。 因此我们还需三到五年 才能开始人体试验。 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。 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。
Thank you.
谢谢大家。
(Applause)
(掌声)