Small molecule-based strategies are often effective for treating human diseases caused by an excess of protein function. However, these small molecule-based strategies are ineffective for treating diseases caused by a deficiency of protein function. Given all of the advantageous therapeutic features of small molecules, it would be highly impactful if small molecules also possessed the ability to autonomously replicate the function of proteins. Small molecules have been shown to at least partially replicate many of the sophisticated functions of proteins, but it is currently uncertain if this partial replication can be adequate to restore the health of a living system. We herein report restoration of cell growth upon treating a growth-deficient strain of yeast which lacks a highly selective, inwardly rectified, and tightly regulated ion transporter protein with an intrinsically less selective, directionless, and unregulated ion channel formed by the small molecule amphotericin B. Furthermore, the restoration of cell growth is both robust and sustainable for over a month. This finding illustrates that small molecule-based partial replication of protein function can have a high impact on the health of a living system. These results encourage the potential of treating currently incurable human diseases with small molecules that replicate the functions of proteins, thereby acting as molecular prosthetics.

Functional complementation of a deficient protein with a small molecule restores cell physiology

246th National Meeting (2013)

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