2.00pm – 3.00pm

IMRE, Kinesis Building,

Seminar Room 1, Level 5

Speaker: Prof. Bradley L. Pentelute, Associate Professor of Chemistry, Massachusetts Institute of Technology

Host : Dr. Kedar Hippalgaonkar, Electronic Materials Department, IMRE

Abstract

Antisense oligonucleotides, proteins and other biopolymers serve as a foundation of modern therapeutics for the treatment of diseases ranging from cancer to diabetes. The discovery, manufacturing, and delivery of these biomolecules into cells is often a challenge and limits rapid translation to the clinic. Here I describe our latest findings on the development of a platform for discovery of peptide drug leads from 100 million-member synthetic libraries. Our best lead compounds efficiently disrupt cancer-specific protein-protein interactions in cells. We also aim to overcome the cytosolic delivery barrier with cell-penetrating peptides, chemical vectors that facilitate cellular permeation and nuclear targeting of antisense cargoes. The properties of these peptide-based materials were positively altered with macrocyclization chemistry, specifically by cysteine arylation. These modifications impart the ability to cross biological barriers, including the blood-brain barrier and plasma membrane, allowing the therapeutic biopolymers to strike their target and correct cellular function. We applied machine learning algorithms to our vast data set on cellular penetration and predicted novel peptide materials to transport into cells large oligonucleotides (6,500 Da) that may treat Duchenne muscular dystrophy. Manufacturing our new cell-penetrating drug leads and oligonucleotides is hindered by the rate at which we synthesize them, which is far slower than Nature’s production pace of seconds. Realizing this, we have built table top machines that that use man-made chemistry to synthesize peptides in minutes and proteins in hours. Our next steps are to layer on reinforcement learning to each of these platforms while introducing them to clinicians, enabling the rapid advancement of innovative medicines into clinical trials.

About the speaker

Bradley L. Pentelute, Associate Professor of Chemistry. He is also an Associate Member, Broad Institute of Harvard and MIT, an Extramural Member of the MIT Koch Cancer Institute, and Member, Center for Environmental Health Sciences MIT. He received his undergraduate degree in Psychology and Chemistry from the University of Southern California, and his M.S and Ph.D. in Organic Chemistry from the University of Chicago with Prof. Steve Kent.  He was a postdoctoral fellow in the laboratory of Dr. R. John Collier at Harvard Medical School, Microbiology.

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For further enquiries, please contact Dr Kedar Hippalgaonkar ( kedarh@imre.a-star.edu.sg)