<p>This book focuses on the chemical synthesis and functional evaluations of several protein domains of therapeutic importance.&#xa0; 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.</p><p>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.&#xa0; 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.</p><p>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.</p>