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.
我是蛋白質設計師。 我想要談的是一種新的藥物。 它是由一種分子製造, 叫做拘束胜肽。
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.
現今只有少數幾種拘束胜肽藥物, 但在接下來十年會有 更多出現在市場上。 咱們來探討這些新藥品 怎麼製成、有何不同, 以及是什麼原因造成 這波另人興奮的新藥浪潮。
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.
拘束胜肽是非常小的蛋白質。 它們有額外的化學鍵 可以拘束分子的形狀, 因此它們非常穩定, 同時效力也非常強。 它們是天然的,人體就會產生幾種, 能協助我們對抗細菌性、 霉菌性,和病毒性感染。 蛇和蝎子這些動物 在毒液中就有拘束胜肽。
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.
用蛋白質做成的藥物稱為生物藥。 生物藥包括拘束胜肽, 以及胰島素這類藥物, 或是阿達木單抗、 依那西普等抗體藥物。 一般來說,生物藥很好, 因為它們有好幾種機制 可以避免掉藥物造成的副作用。
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,蛋白質。 它是我們體內完全天然、 無毒性的材料。 我們的細胞會產生 數萬種不同的蛋白質, 我們所有的食物 基本上都含有蛋白質。 第二,有時, 一般藥物在體內會和分子 發生你不想要的作用。 相較於小分子藥物, 我指的是一般藥物,如阿斯匹靈, 生物藥算是相當大的。
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.
分子的形狀能完美符合時 就會發生交互作用。 很像鎖和鑰匙。 比較大的鑰匙有比較多溝槽, 所以比較有可能符合一個鎖。 但,大部分的生物藥都有個瑕疵。 它們很脆弱。 所以通常會用注射的, 因為如果用吃的, 胃酸會破壞這種藥。 拘束胜肽則相反。
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.
它們的耐受度跟一般藥物一樣強。 所以是有可能用藥丸、吸入器、 軟膏的方式來服用塗抹這類藥物。 這就是為什麼在藥物發展上 拘束胜肽十分讓人滿意。 它們把小分子和生物藥的優點 都結合在一起了。 但,不幸的是,我們非常難將 大自然中找到的拘束胜肽 重新再造為新藥物。
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.
於是該我登場了。 創造新藥物很像是針對某個鎖 刻出符合的鑰匙。 我們必須要把形狀做對。 但,若把拘束胜肽的 形狀改變太多, 那些額外的化學鍵就無法形成, 整個分子就會崩壞。 所以我們必須要想辦法 控制它們的形狀。
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.
我參與了一項科學合作計畫, 橫跨三個國家十多個機構, 大家集結起來要解決這個問題。 我們根據先前經驗採用了 一個非常不同的方式。 我們不是去改變 在大自然中找到的拘束胜, 我們是想辦法從無到有 打造出新的拘束胜肽。 為此,我們開發了 開放程式碼的胜肽設計軟體, 讓任何人都可以自由取用來做設計。
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.
為了測試我們的方法, 我們先生成一系列的拘束胜肽, 有各式各樣的形狀。 當中有許多是 大自然中前所未見的。 接著,我們進入實驗室, 製造出這些肽。 然後,我們用實驗 來決定它們的分子結構, 把我們設計的模型 和真實的分子結構做比較後, 我們發現,我們的軟體 可以定位個別原子, 且精準到超過能測量的極限。 三年前,這還是不可能的。 但,現今,我們有能力 可以創造出客製化的胜肽, 可以客製化它們的形狀做藥物開發。
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.
這項技術會引領我們到哪裡? 最近,我和同事設計出的拘束胜肽 能夠殺死流感病毒、 避免肉毒中毒, 及阻擋癌症細胞生長。 其中一些新藥物已經 用實驗室動物做過臨床前試驗, 目前,它們都很安全且非常有效。
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.
拘束胜肽設計是一項先進技術, 而藥物開發的過程既緩慢又謹慎。 所以還要三到五年才能做人體試驗。 但,在那期間, 會有更多拘束胜肽藥物 進入藥物開發過程。 最終,我相信客製化的拘束胜肽藥物 將讓我們有能力擺脫疾病的拘束。
Thank you.
謝謝。
(Applause)
(掌聲)