This is a line of research that will come to be increasingly important as it new technologies make it ever easier and more cost effective to both identify specific components of the protein machinery of biology and manufacture replacements or augmented alternative versions. It is not just important for genetic diseases, in which specific proteins are missing or malformed, but also in patching over the changes of aging and enhancing the human body to better resist aging:
"Artificial limbs replace the function of an arm or leg that's missing due to injury. Some diseases occur because proteins in the body are missing or not working properly. Molecular prosthetics envisions treating those diseases with medicines that replace the functions of the missing proteins."
[Researchers] described advances to simplify and speed up the synthesis of the small molecules needed for molecular prosthetics. More than 90 percent of today's medicines use active ingredients that are small molecules. These substances can be processed into tablets and capsules and taken by mouth. They can dissolve in the gastrointestinal tract, go into the blood and travel to and work in almost every part of the body. The rest of today's medicines are large molecules or "biologics" that like insulin cannot be taken by mouth.
"For molecular prosthetics to become a reality, we must overcome two major challenges. First, it can take months or even years to synthesize just one molecule. With our new platform, we could reduce that to a few days. The second challenge is to fundamentally understand the capacity for small molecules to operate like proteins in the context of living systems. That understanding is critical to being able to design the most effective molecules."
Amphotericin B, currently used to treat fungal infections, [inserts] itself into the membrane that surrounds and encloses cells in the body. Once in the membrane, amphotericin B forms channels that enable the transport of ions into and out of the cell, an activity that mirrors many proteins whose function is critical in health and disease. A whole group of human diseases, sometimes called channelopathies, result from malfunction of ion channel proteins. Among them: migraine, epilepsy and cystic fibrosis. The team is working to use amphotericin B as a basis for making small molecules that replace the missing or malfunctioning ion channel proteins and thereby treat these diseases.
"We realized early in our studies that the lack of efficiency and flexibility with which small molecules can be prepared in the lab represented a major bottleneck in our efforts to develop small molecules with protein-like functions. We are now excited to find that our new synthesis platform can help relieve this important bottleneck and thereby enable us to focus more of our time on the key functional studies. Drug companies also have this problem with the long timelines needed to synthesize small molecules. That's part of the reason why it takes so long to develop new medicines. This is a broad problem, and our goal is to help speed up this process and thereby have an important impact on science and medicine."