Automated Drug Discovery - Burke Group

Date

03/01/15

A new molecule-making machine could do for chemistry what 3-D printing did for engineering: Make it fast, flexible and accessible to anyone.

Chemists at the University of Illinois, led by chemistry professor and medical doctor Martin D. Burke, built the machine to assemble complex small molecules at the click of a mouse, like a 3-D printer at the molecular level. The automated process has the potential to greatly speed up and enable new drug development and other technologies that rely on small molecules.

"We wanted to take a very complex process, chemical synthesis, and make it simple," said Burke, a Howard Hughes Medical Institute Early Career Scientist. "Simplicity enables automation, which, in turn, can broadly enable discovery and bring the substantial power of making molecules to nonspecialists."

The researchers described the technology in a paper featured on the cover of the March 13 issue of Science.

"Small molecules" are a specific class of complex, compact chemical structures found throughout nature. They are very important in medicine – most medications available now are small molecules – as well as in biology as probes to uncover the inner workings of cells and tissues. Small molecules also are key elements in technologies like solar cells and LEDs.

However, small molecules are notoriously difficult to make in a lab. Traditionally, a highly trained chemist spends years trying to figure out how to make each one before its function can even be explored, a slowdown that hinders development of small-molecule-based medications and technologies.

"Up to now, the bottleneck has been synthesis," Burke said. "There are many areas where progress is being slowed, and many molecules that pharmaceutical companies aren’t even working on, because the barrier to synthesis is so high."

The main question that Burke’s group seeks to answer: How do you take something very complex and make it as simple as possible?

The group’s strategy has been to break down the complex molecules into smaller building blocks that can be easily assembled. The chemical building blocks all have the same connector piece and can be stitched together with one simple reaction, the way that a child’s interconnecting plastic blocks can have different shapes but all snap together. Many of the building blocks Burke’s lab has developed are available commercially.

See a video of Burke explaining the process.

To automate the building-block assembly, Burke’s group devised a simple catch-and-release method that adds one building block at a time, rinsing the excess away before adding the next one. They demonstrated that their machine could build 14 different classes of small molecules, including ones with difficult-to-manufacture ring structures, all using the same automated building-block assembly.

"Dr. Burke’s research has yielded a significant advance that helps make complex small molecule synthesis more efficient, flexible and accessible," said Miles Fabian of the National Institutes of Health’s National Institute of General Medical Sciences, which partially funded the research. "It is exciting to think about the impact that continued advances in these directions will have on synthetic chemistry and life science research."

The automated synthesis technology has been licensed to REVOLUTION Medicines, Inc., a company that Burke co-founded that focuses on creating new medicines based on small molecules found in nature. The company initially is focusing on anti-fungal medications, an area where Burke’s research has already made strides.

"It is expected that the technology will similarly create new opportunities in other therapeutic areas as well, as the industrialization of the technology will help refine and broaden its scope and scalability," Burke said.

"Perhaps most exciting, this work has opened up an actionable roadmap to a general and automated way to make most small molecules. If that goal can be realized, it will help shift the bottleneck from synthesis to function and bring the power of making small molecules to nonspecialists."

Scientific American article - Machine Stitches Complex Molecules at Touch of a Button

UIUC'c News Bureau article, author - Liz Ahlberg

Photo by L. Brian Stauffer

Related People

Directory

scheelinAlexander
Scheeline
bjmccallBenjamin
McCall
cmartn10Calgary
Martin
r-gennisRobert
Gennis
j-gerltJohn
Gerlt
sgranickSteve
Granick
mgruebelMartin
Gruebele
hergenroPaul
Hergenrother
huangRaven
Huang
mlkraftMary
Kraft
leckbandDeborah
Leckband
yi-luYi
Lu
martinisSusan
Martinis
snairSatish
Nair
eoldfielEric
Oldfield
rienstraChad
Rienstra
cmsCharles
Schroeder
zanZaida
Luthey-Schulten
sksScott
Silverman
s-sligarStephen
Sligar
zhao5Huimin
Zhao
mselfba2Michelle
Self-Ballard
pbraunPaul
Braun
mdburkeMartin
Burke
jeffchanJefferson
Chan
sdenmarkScott
Denmark
dlottDana
Dlott
foutAlison
Fout
agewirthAndrew
Gewirth
ggirolamGregory
Girolami
shs3Sharon
Hammes-Schiffer
sohirataSo
Hirata
kamihullKami
Hull
jainPrashant
Jain
jkatzeneJohn
Katzenellenbogen
nmakriNancy
Makri
douglasmDouglas
Mitchell
jsmooreJeffrey
Moore
murphycjCatherine
Murphy
r-nuzzoRalph
Nuzzo
dimerPhilip
Phillips
rauchfuzThomas
Rauchfuss
joaquinrJoaquín
Rodríguez-López
jrogersJohn
Rogers
sarlahDavid
Sarlah
kschweizKenneth
Schweizer
jsweedleJonathan
Sweedler
vddonkWilfred
van der Donk
renskeRenske
van der Veen
vuraweisJosh
Vura-Weis
mcwhite7M.
White
sczimmerSteven
Zimmerman
beakPeter
Beak
wklemperWalter
Klemperer
jdmcdonaJ.
McDonald
mvp11Michael
Pak
pogoreloTaras
Pogorelov
mshen233Mei
Shen
dewoonDavid
Woon
wboulangWilliam
Boulanger
rxbRohit
Bhargava
qchen20Qian
Chen
jianjuncJianjun
Cheng
hy66Hong
Yang
andinomaJosé
Andino Martinez
decosteDonald
DeCoste
thhuangTina
Huang
tjhummelThomas
Hummel
dkellDavid
Kell
doctorkMichael
Koerner
marvilleKelly
Marville
crrayChristian
Ray
tlbrownTheodore
Brown
rmcoatesRobert
Coates
thdjrThom
Dunning,
dykstraClifford
Dykstra
j-jonasJiri
Jonas
j-lisyJames
Lisy
shapleyJohn
Shapley
pshapleyPatricia
Shapley
awieckowAndrzej
Wieckowski
zumdahl2Steven
Zumdahl
ksuslickKenneth
Suslick
jlbearJodi
Bear
jcoxJenny
Cox
ealthausEllen
Althaus
staciryStaci
Ryan
sqdSean
Drummond
dmillsDouglas
Mills
sheeleySarah
Sheeley
jsmaddenJoseph
Madden
cknight4Connie
Knight
schulzeHeather
Schulze
slangleySamantha
Langley
ssmurrayStar
Murray
kbaumgarKeena
Finney
adkssnBeatrice
Adkisson
bmylerBeth
Myler
trabari1Katie
Trabaris
kewatsonKaren
Watson
strussTheresa
Struss
metclfKara
Metcalf
ljohnso2Lori
Johnson
jlwJamison
Lowe
jenruslJennifer
Russell
lchenoweLeslie
Chenoweth
jcfJonathan
Freiman
wdedoWolali
Dedo
ebielserElaina
Kutz
spinnerDavid
Spinner
plblumPatricia
Simpson
stevens2Chad
Stevens
lsagekarLori
Sage-Karlson
bertholdDeborah
Berthold
kecarlsoKathryn
Carlson
tlchen4Timothy
Chen
sdesmondSerenity
Desmond
angelaecAngela
Crawford
hsahmed3Hajira
Ahmed
kakinsKenye
Akins
asali3Arzeena
Ali
axelson2Jordan
Axelson
bai11Yugang
Bai
scbakerStephanie
Baker
duffin2Kevin
Duffin
duttadDebapriya
Dutta
pflotschPriscila
Falagan Lotsch
iflemingIan
Fleming
dgrayDanielle
Gray
thennes2Thomas
Hennessey
mhettingMary Jo
Hettinger
holdaNancy
Holda
holler2Jordan
Holler
aibarrAlejandro
Ibarra
kimshSung Hoon
Kim
kocherg2Nikolai
Kocherginsky
philipk2Philip
Kocheril
dlee106David
Lee
legare2Stephanie
Legare
alewandoAgnieszka
Lewandowska
qianliliQianli
Li
bdmccallBirgit
McCall
smccombiStuart
McCombie
jdm5Justin
McGlauchlen
egmooreEdwin
Moore
myerscouKathleen
Myerscough
snalla2Siva
Nalla
oraham2Aaron
Oraham
lah5LeeAnn
Pannebaker
poonawa2Maria
Poonawalla
rrollerR.
Roller
romanovaElena
Romanova
roubakhiStanislav
Rubakhin
vsfVictoria
Shepherd-Fortner
shvedalxAlexander
Shved
asoudaAlexander
Soudakov
ktsween2Kalee
Sweeney
sktarterSamantha
Tarter
aathoma2Andy
Thomas
kwilhelKaren
Wilhelmsen
wilkeyRandy
Wilkey
luxu3Lu
Xu
yuanyao4Yuan
Yao
silongSilong
Zhang
schlembaMary
Schlembach
emccarr2Elise
McCarren
cmercierChristen
Mercier