Development of an Albumin-Masked mutPD-1Ig as a Tumor Lesion-Selective Immune Checkpoint Inhibitor.

The antitumor effects elicited by immune checkpoint inhibitors (ICIs) have transformed cancer treatments. However, severe immune-related adverse events (irAEs) resulting from these treatments have restricted the application of ICIs. To overcome the adverse events, we developed a tumor lesion-selective pro-PD-1Ig that is activated by proteases overexpressed in tumors.

A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.

Background: CTLA4Ig is a dimeric fusion protein of the extracellular domain of cytotoxic T-lymphocyte protein 4 (CTLA4) and an Fc (Ig) fragment of human IgG that is approved for treating rheumatoid arthritis. However, CTLA4Ig may induce adverse effects. Developing a lesion-selective variant of CTLA4Ig may improve safety while maintaining the efficacy of the treatment.

Sensing HIV Protease and Its Inhibitor Using "Helical Epitope"-Imprinted Polymers.

A helical epitope-peptide (lle-Gly) was selected from the α-helix structure of the HIV protease (PR) as the template, which represents an intricate interplay between structure conformation and dimerization. The peptide template was mixed with water, trifluoroethanol (TFE), and acetonitrile (ACN) at a certain ratio to enlarge the helical conformation in the solution for the fabrication of helical epitope-mediated molecularly imprinted polymers (HEMIPs) on a quartz crystal microbalance (QCM) chip. The template molecules were then removed under equilibrium batch rebinding conditions involving 5% acetic acid/water.

Modulation of substrate specificities of D-sialic acid aldolase through single mutations of Val-251.

In a recent directed-evolution study, Escherichia coli D-sialic acid aldolase was converted by introducing eight point mutations into a new enzyme with relaxed specificity, denoted RS-aldolase (also known formerly as L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase), which showed a preferred selectivity toward L-KDO. To investigate the underlying molecular basis, we determined the crystal structures of D-sialic acid aldolase and RS-aldolase. All mutations are away from the catalytic center, except for V251I, which is near the opening of the (α/β)(8)-barrel and proximal to the Schiff base-forming Lys-165.