What is Chemical Biology?  Perhaps it’s Peptidomimetics
May02

What is Chemical Biology? Perhaps it’s Peptidomimetics

Disclaimer: I am not an expert. In fact, this series of blog posts is as informative  to me as it is to you. Probably even more so. My views and the views of people interviewed for this blog do not, in fact, reflect what exactly “chemical biology” is, but only a snapshot.  Please direct any comments or suggestions below! Peptidomimetics is something I think about all the time.  So, I decided it would be a pretty good starting point for this series, especially considering that right now it’s finals week and I barely have enough time to be running a synthesis, much less studying for finals.  But that’s beside the point, because I’m very excited to learn more about peptidomimetics (and who needs to study for finals when you can do research instead, am I right?)! What is peptidomimetics?   From what I’ve seen, it’s pretty much exactly how it sounds.  The essential goal of the field is to take a peptide of interest, which usually means that it’s bioactive or important in some way physiologically, and synthesize and test organic mimics of it to fulfill a number of different goals.  So if we have bioactive peptides why not just use them as drugs?  Because peptides have some inherent problems to their usage that peptidomimetics seeks to solve: Protease Resistance/Serum Stability:  One of the main reasons that peptide drugs (mainly mimics of allosteric regulators) have been largely unsuccessful.  When a peptide is taken up by the body, either intravenously or orally, the body has a suite of enzymes (such as proteases and E3-Ubiquitin Ligases) which degrade small peptides and foreign ingested proteins.  While these processes are important in metabolism and immune function, we would rather our peptides not be degraded by the body.  One of the main goals of peptidomimetics is to avoid the body’s natural defense against peptides and to get at biological targets. Membrane permeability:  Most biological targets are located inside cells.  In order to get your favorite peptide into a cell, you need to cover it with lipophilic groups (or else somehow reduce the charge) to help it squeegee its way (technical term) into the cell.  Small molecules, being generally much smaller, rigid, and lipophilic, rarely have this problem.  Because peptides routinely break Lipinski’s Rule of Five for drug-likeness, special provisions must be taken in synthesis and design. Conformational Restriction:  Very often, peptides are considered “floppy.”  They require an optimal “active conformation” to bind to or inhibit other enzymes.  Very often, peptidomimetics seeks to modify peptides by constraining them into a more stable and active conformation, thus reducing the entropic cost of a peptide’s action. So what kind...

Read More
What is Chemical Biology?  No… seriously.
Apr25

What is Chemical Biology? No… seriously.

Disclaimer: I am not an expert. In fact, this series of blog posts is as informative  to me as it is to you. Probably even more so. My views and the views of people interviewed for this blog do not, in fact, reflect what exactly “chemical biology” is, but only a snapshot.  Please direct any comments or suggestions below! The next several months are pretty big for me.  Soon, I’ll be taking the GRE and deciding where to go for my PhD, but I honestly have no idea where I want to study.  Because of my current research and classes I’ve taken, I know that Chemical Biology is the field for me.  The only issue is, when asked recently by friends, family, and random strangers  what Chemical Biology really is, I’m kind of at a loss. For me, Chemical Biology means probing biological systems with chemical agents.  Recently, I’ve had a chance to talk to a couple PhD candidates (including our very own  Christine Herman) in Chemical Biology, and they all had varied definitions.  Christine’s and my research could not be more different; she does research in bioassays, and I do a lot of work in peptidomimetics and drug discovery.  Her research is in the analytical department, and mine in the organic.  It surprised me to learn that she classified herself as a chemical biologist as well.  This led me to a couple conclusions: Chemical Biology is less of a specific field but more of a classification encompassing a wide range of different kinds of research.  Things that would have once been considered organic chemistry (such as what I do), analytical chemistry (what Christine does), or even physical chemistry (see some later posts!) are now under the great big umbrella that is Chemical Biology.  So, what’s a young blogger to do?  Over the next several months, I’m going to examine different areas of research in Chemical Biology, one by one.  I’m planning on getting in touch with some of the leaders in field.  Hopefully, this will be fun for everyone, and help me decide where I want to do my PhD. Next Monday tune in for a subject near and dear to my heart:  peptidomimetics!  Any suggestions on who to talk to?  Post...

Read More