A circular exploration of cryoprotective agents for stem cells using computer-aided molecular design approaches

Abstract

This work presents a circular exploration of cryoprotective agents (CPAs) for stem cells using computer-aided molecular design approaches that can comprehensively consider compounds. An exploration cycle was developed that consists of the following five steps: setting conditions, computational evaluation, experimental evaluation, verification experiments, and discussions with experts in biotechnology. It aims to discover promising CPA candidate compounds by incorporating domain knowledge through discussions with the experts. The developed cycle can be applied to fields where the required physical properties have not been clearly known. As a result, 1-methylimidazole and pyridazine were selected as promising CPA candidate compounds, which were both heterocyclic amines. Hence, heterocyclic amines could be a stepping-stone toward the future development of CPAs for stem cells. By repeatedly using the exploration cycle, CPA candidate compounds with better cryoprotective effects could be discovered.