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Computational studies of effects of surface charge on biomembrane and membrane permeability of molecules

高橋, 輝行 筑波大学 DOI:10.15068/0002005503

2022.11.17

概要

Drugs that maintain human health have been of great interest in life science. Since ancient times, drugs have been used through medicinal herbs. For example, the antipyretic properties of willow bark have been known since the time of the ancient Greeks and Romans, and it has been widely used as a medicine in many parts of the world since then. In 1897, Felix Hoffmann of Bayer AG isolated the active ingredient from willow bark that was responsible for the antipyretic effect and named it salicin. The molecular structure of salicin was also elucidated. Later, in order to increase the efficacy of salicin, a derivative with a modified side chain was produced and named Aspirin (Ref. 1-1). Aspirin is still a useful drug used worldwide as an antipyretic analgesic and rheumatism medicine. Since then, not only aspirin, but also other drugs have been developed by changing the side chains of existing drug molecules to enhance their efficacy, which has been a major research method for a long time.

 Altering chemical groups toward lead compounds has been used mainly for small molecule drugs that are easy to synthesize and modify chemically, and these small molecule drugs are drugs with a molecular weight of 500Da or less. From the 1980's to the early 2000's, the development of these small molecule drugs was actively pursued mainly in the field of lifestyle-related diseases such as hypercholesterolemia, hypertension, and diabetes.

 However, because they are the small molecules, there is a limit to the number of derivatives that can be made, and it was soon said that there was a limit to the development of new small-molecule drugs. Since the 2000s, antibody drugs with large molecular weights have played a leading role in the development of new drugs, and of course, because of their large molecular weights, it is possible to create a variety of drugs by modifying them suitable for target proteins. Nevertheless, the cost of development is enormous, leading to increased medical costs and disparities in medical care. On the other hand, middle-sized molecules, which are intermediate in size between small molecules and antibodies, receive much attention from experimental and theoretical viewpoints, but in any case, there are high expectations for new drugs for modification.

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Chapter 5

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