Changing relations between proteins and osmolytes: a choice of nature

Many studies aimed at advancing our understanding of the mechanisms of protein stabilization that support the survival of organisms under harsh environmental conditions are focused on deciphering the role of osmolytes as additives in the stabilization of protein. The exact interaction of an osmolyte with protein has been a matter of debate for a long time, but a clear unifying statement still cannot be provided regarding the actual behavior of the osmolyte. A literature survey reveals that there exist a large number of scholarly articles as well as elegant reviews that could aid a resolution of some problems of understanding systems comprising osmolytes and proteins. Additionally, there is no doubt from a vast literature survey that osmolytes display stabilizing behavior toward proteins. However, there are also a number of research articles available in the open literature that emphasize the destabilizing effects of osmolytes on protein stability and function. Therefore, a complete acquaintance of each osmolyte with respect to each protein is one of the most challenging tasks in the development of protein formulation and may be still needed in order to reliably administer the correct protein formulations through injection only. The lack of a comprehensive evaluation of a broad range of these osmolytes in protein systems stimulated our interest for the present perspective in this research field. To the best of our knowledge, this perspective delineates the most recent successful advances in the open literature and also on the basis of our research experience and should aid current researchers in the field of protein stabilization to develop new strategies.