Synthesis of Functional Characterization of Protein Domains for the Development of Mirror-Image Therapeutics

This book focuses on the chemical synthesis and functional evaluations of several protein domains of therapeutic importance.  The mirror-image protein domains, which can be prepared by chemical synthesis, are useful for the development of mirror-image protein therapeutics with low immunogenicity.

This book first describes the preparation of two protein domains of therapeutic targets, the extracellular domain of T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), and human serum albumin domain III.  The bioactivities and functions of these synthetic protein domains were confirmed by analyzing the interaction with their protein ligands and molecular probes. The mirror-image forms of these protein domains are applicable to screening campaigns by mirror-image phage display technology. Second, the design and synthesis of a novel variant of monobody, an antibody-like protein domain, are described. The monobody variant was prepared by facile synthetic procedures, enabling the practical synthesis of less-immunogenic mirror-image monobody. The variant was additionally applied to a structure–activity relationship study to explore the appropriate chemical modification for a superior monobody scaffold with improved stability and binding affinity.

These data of the synthesis and evaluation of the protein domains in this book provide an important resource for studies on functional mirror-image protein domains for next-generation protein therapeutics.