Biologically Functional Control Molecules Born from a Double Major and a Frontier Spirit

Kazutoshi Toshima (Professor, Department of Applied Chemistry)

Have you ever heard the phrase "making drugs"? In Japanese, there are two ways to write the verb "to make" (tsukuru): 作る and 創る. Although they are pronounced the same, their meanings are quite different. Both verbs mean "to produce a desired object by processing materials," but 創る (to create) carries the additional nuance of making something "new" or "for the first time." In our laboratory, we are actively engaged in research that both "makes" (作る) and "creates" (創る) "biologically functional control molecules," such as drugs.

So, what is necessary to "create" these biologically functional control molecules? Since we are "creating" the first-ever, new, so-called original molecules, the first requirement is "molecular design" to determine what kind of molecule to create. Today, this is often done using computer-based molecular simulations. However, the biologically functional control molecules conceived at this stage are, so to speak, a pie in the sky. The next step is to make them a reality. We use "organic synthetic chemistry" to synthesize the target molecule and actually hold it in our hands. It is quite a challenge to create a designed molecule from scratch, but even after obtaining it, the process is not over. We need to analyze and evaluate whether the molecule we have obtained has the desired function as designed. In the case of biologically functional control molecules, this requires using various techniques from "biochemistry" and "cell biology" to analyze and evaluate their function. Of course, the results may show that the molecule we worked so hard to create does not have the desired function. In that case, we use that knowledge to lead to a new "molecular design." Do you see the pattern? Research to "create" original biologically functional control molecules requires a cycle with a series of steps: "molecular design" → "organic synthetic chemistry" → "biochemistry" → "cell biology." For this reason, a single academic field, such as "chemistry" for making things or "biology" for analyzing functions, is not enough. The fusion of "chemistry" and "biology"—in other words, a "double major"—is essential. Furthermore, a "frontier" spirit to aim for original biologically functional control molecules with new functions that no one has ever created before, and the pioneering of "frontier" areas to make this possible, are naturally required.

To date, our laboratory has been strongly conscious of this research policy and has produced a variety of "biologically functional control molecules." A particular focus is the "creation of molecules for photocontrolling biological functions," which incorporates the "physical" element of light in addition to "chemistry" and "biology." These molecules enter cells, and when irradiated with light of a specific wavelength, they decompose nucleic acids, proteins, and glycans related to various diseases, thereby controlling their functions. Moreover, they can precisely control only the targeted function from both temporal and spatial perspectives. Specifically, "molecules for photocontrolling biological functions" have been created that suppress the proliferation of breast cancer cells, inhibit HIV replication, evade the toxicity of amyloid-beta to enable the survival of nerve cells, suppress the activity of drug-resistant influenza enzymes, and even inhibit the growth of Mycobacterium tuberculosis. These are now undergoing further applied development.

We grow attached to these "biologically functional control molecules," born from our own creativity and ingenuity, as if they were extensions of ourselves, or even our own children. Based on a research style driven by the spirit of a "double major" and the "frontier," we aim to create our own original "biologically functional control molecules"! Embracing this dream, we dedicate ourselves to our research every day.