Protein Prenylation: the Anchor of Life

MDD Group Spring 2019

What is Protein Prenylation?

Protein prenylation is a post-translational modification that consists of the attachment of 15 or 20 carbon isoprenoids to specific cysteine residues positioned near the C-termini of proteins.  In a eukaryotic cell, there are several hundred prenylated proteins including most members of the Ras superfamily and heterotrimeric G-proteins; the prenyl group serves to anchor these proteins in the membrane so that they are positioned to interact with cell surface receptors either directly or via adaptor proteins.  This means that essentially all signaling processes in eukaryotic cells require the participation of prenylated proteins for everything ranging from the regulation of cell division to stem cell differentiation and development.  Beyond biological significance, the critical role of prenylated proteins also makes them important targets for the design of new therapeutic agents for a variety of diseases


Research in the Distefano Group

Work in the Distefano Group on protein prenylation is focused in two areas: Chemical Biology and Biotechnology Applications.  In pursuit of those studies, members of the group perform a variety of different types of experiments including chemical synthesis, biochemistry, proteomics and cell culture and animal-based work.  The goal of this work is to gain insight into protein prenylation that can be used to advance biology and develop new therapeutic approaches for a broad range of diseases including cancer, Alzheimer’s disease and infectious disease.

Group News

New photoremovable protecting group reported

In a recent manuscript published in Organic and Biomolecular Chemistry, Graduate student Mohsen Mahmoodi in collaboration with the Blank group describe a new coumarin-based protecting group (mBhc) that can be used for thiol caging...

Jeff Vervacke defends Ph.D. thesis

On Thursday 5/5, Jeff Vervacke defended his thesis entitled "Small Molecules and Functionalized Peptides to Study Protein Prenylation".  In the course of his Ph.D. work, Jeff has worked on a wide range of peptide-related projects.  Beyond his work on protein prenylation, Jeff has also worked on the preparation of peptides for vaccine development and for the study of DNA repair.

Mohsen Mahmoodi's paper on NDBF thiol protection accepted in JACS

Graduate student Mohsen Mahmoodi's paper titled "Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to Brominated Hydroxycoumarin for Thiol Caging in Peptides" was accepted in the Journal of the American Chemical Society.  This manuscript describes the use of NDBF protection for thiols to allow one- and two photon uncaging of peptides to be performed in vitro and in live cells.  This allows thiol mediated events to be rapidly triggered with high efficiency.