D-amino acids in protein de novo design. II. Protein-diastereomerism versus protein-enantiomerism

With a few exceptions, proteins in our biosphere are based exclusively on L-amino acids. The inversion of configuration of all the stereogenic centers in a protein leads to an all-D compound with 'mirror image' properties and 'mirror image' structure. We propose to use the term protein-enantiomerism to describe the relationship between two proteins that have the same sequence but whose amino acids have opposite configuration. We will use the term protein-diastereomerism to define the relationship between two proteins that have the same sequence in which some amino acids have opposite configurations. A classification of type I, II, III, and IV protein-diastereomerism is proposed. By extension, a diastereoprotein is a protein where some amino acids have the same configuration (L or D) while others have the opposite one (D or L). A particular case of diastereoproteins are mesoproteins, also analyzed in this article. In addition Co the goal of making proteins resistant to protease degradation, the use of D-amino acids in protein de novo design may give rise to proteins with structures, and perhaps properties, very different to those of native all-L-proteins.