Minkui Luo - speaker's webpage
Department of Molecular Pharmacology & Chemistry
Memorial Sloan-Kettering Cancer Center
Host: Jay Groves

Profile Substrates and Inhibitors of Protein Methyltransferases

Epigenetic regulations are involved in establishing cell-lineage diversity and the errors in these processes have been linked to many diseases including developmental abnormalities, neurological disorders and cancer. Among the key biochemical modifications in epigenetics is protein methylation, a process orchestrated by over 60 human protein methyltransferases (PMTs). Profiling targets and inhibitors of the PMTs is pivotal toward elucidating their roles in normal physiology and disease states. Unfortunately, conventional approaches are inefficient in these aspects. To address this challenge, our laboratory has developed a novel technology, which we termed as Bioorthogonal Profiling of Protein Methylation (BPPM). Here we engineered the SAM-binding pockets of designated PMTs to accommodate bulky SAM analogues. The engineered PMTs then tag distinct chemical moieties to the substrates of the designated PMTs, in conjunction with click chemical ligation, for target identification. To develop PMT inhibitors aiming at both potency and specificity, we combined rational design and high throughput screening approaches. Our transition-state analogue inhibitors show high potency against multiple PMTs. The biological evaluations of these inhibitors as chemical probes or anti-cancer reagents are ongoing.

Erik Sorensen - group webpage
Haw Yang - group webpage
Dorothea Fiedler - group webpage

Faculty Research Talks with Professors Erik Sorensen, Haw Yang and Dorothea Fiedler. Departmental and Alumni reception to follow in Taylor Commons, including graduate awards presentation, 3:00 - 4:30 pm.

Frick tours available.

Kathryn Wagner, lecture demonstrator, will present a program of chemical demonstrations for the entire family, including some popularized by the late Professor Hubert Alyea ‘24 *28. Light refreshments to follow in the Taylor Auditorium Lobby.

Frick tours available.