Jeg er en proteindesigner. Og jeg vil gerne diskutere en ny type medicin. Den er lavet af et molekyle kaldet et begrænset peptid.
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.
Der er kun få begrænset peptid mediciner tilgængelige i dag, men der er mange som vil ramme markedet i det kommende årti. Lad os udforske hvad de nye mediciner er lavet af hvordan de er anderledes and hvad skyldes denne voksende bølge af nye og spændende mediciner.
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.
Begrænset peptider er meget små proteiner. De har ekstra kemiske forbindelser som begrænser formen af molekylet, og dette gør dem utrolig stabile lige så vel som meget stærke. De opstår naturligt, vores kroppe producerer faktisk enkelte som hjælper med at angribe bakterier, svamp og virus sygdom Og dyr ligesom slanger og skorpioner bruger begrænset peptider i deres gift.
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.
Medicin som er lavet af protein bliver kaldt biologisk medicin. Så dette inkluderer begrænset peptider, og medicin som insulin og antistof medicin som Humira eller Enbrel. Overordnet, biologiske lægemiddler er fantastiske, fordi de undgår flere veje hvor medicin kan skabe bivirkninger.
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.
Først, protein. Det er et totalt neutralt, giftfrit materiale i vores krop. Vores celler producerer tusinde af forskellige proteiner, og, praktisk talt, alt vores mad har proteiner i det. Og anden, nogle mediciner interagerer med molekyler i din krop som du ikke vil have dem til. Sammenlignet med små-molekyle medicin, Og her mener jeg, normal medicin, som aspirin, biologisk medicin er ret stort.
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.
Molekyler interagerer når de påtager forme som passer sammen perfekt Ligesom en nøgle og en lås. Altså, en stor nøgle har mange riller, så det er mere sandsynligt at den passer i en enkelt lås. Men de fleste biologiske mediciner har også en fejl. De er skrøbelige Så de er normalt givet med en indsprøjtning, da vores mavesyre ville ødelægge medicinen hvis vi slugte den.
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.
Begrænset peptider er modsat. De er stærke ligesom normal medicin Så det er muligt at administrer dem med piller, inhalere, og creme. Det er dette som gør begrænset peptider så eftertragtet i medicinsk fremstilling. De kombinerer de bedste funktioner fra små-molekylær og biologisk medicin inden i en. Men desværre er det utrolig svært at ombygge de begrænset peptider som vi finder i naturen til at blive nyt medicin.
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.
Det er her jeg kommer ind. At skabe et nyt medicin er meget ligesom at få en nøgle til at passe i en specifik lås. Vi skal have formen helt rigtig. Men hvis vi ændrer formen af et begrænset peptid for meget kan de kemiske bindinger ikke forbinde og molekylet går i stykker. Så vi bliver nødt til at finde ud af hvordan vi kan kontrollerer formen.
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.
Jeg var en del af en videnskabs indsats spredt over et dusin institutioner fra tre kontinenter som kom sammen og løste dette problem. Vi tog en radikalt anderledes vinkle fra tidligere forsøg. I stedet for at ændre de begrænset peptider som vi finder i naturen, lærte vi at bygge nogle nye fra bunden. For at hjælpe med dette, udviklede vi gratis kildekode peptid-design software som alle kan bruge til dette også.
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.
For at teste vores metode, vi skabte et udvalg af begrænset peptider som har en variation af forskellige forme. Mange af disse havde aldrig været set i naturen før. Så vi gik i laboratoriet og producerede disse peptider. Derefter fandt vi deres molekylære struktur, ved hjæp af eksperimenter. Da vi sammenlignede vores modeller med rigtige molekylære strukturer, fandt vi ud af at vores software kan placere individualle atomer med en præcision som er på grænsen af hvad der er muligt at måle. For tre år siden, dette var ikke muligt. Men i dag har vi evnerne til at skabe designer peptider med forme der er skræddersyet til medicinudvikling.
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.
Så hvor tager den her teknologi os hen? Altså, for nyligt, mine kollegaer og jeg har designet begrænset peptider som neutralisere influenzavirus, beskytter mod botulisme-forgiftning og blokerer kræft celler fra at vokse. Nogle af de nye mediciner er blevet testet i prækliniske forsøg med forsøgsdyr. Og indtil videre er de alle sikre og yderst effektive.
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.
Begrænset peptid design er banebrydende teknologi, og medicinal udvikling er langsomt og forsigtigt. Så vi er stadig tre til fem år væk fra menneske forsøg. Gennem den tid, flere begrænset peptid mediciner kommer til at dukke op i medicinal udvikling. Og jeg tror, at til sidste vil designet peptid mediciner gøre det muligt for os at bryde fri fra begrænsninger af vores sygdomme.
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.
Mange tak.
Thank you.
(Bifald)
(Applause)