Tofacitinib combined with leflunomide for treatment of psoriatic arthritis with IgA nephropathy: a case report with literature review.

Psoriasis is a systemic inflammatory disease that is associated with increased risk of several diseases, such as psoriatic arthritis (PsA), inflammatory bowel disease, and cardiovascular diseases. About 20 to 30% patients with psoriasis subsequently develop PsA. IgA nephropathy is the most common primary glomerular disease world-wide.

Precisely Designed Isopeptide Bridge-Crosslinking Endows Artificial Hydrolases with High Stability and Catalytic Activity under Extreme Denaturing Conditions.

Enzymes normally lose their activities under extreme conditions due to the dissociation of their active tertiary structure. If an enzyme could maintain its catalytic activity under non-physiological or denaturing conditions, it might be used in more applications in the pharmaceutical and chemical industries. Recently, we reported a coiled-coil six-helical bundle (6HB) structure as a scaffold for designing artificial hydrolytic enzymes.

Increase of anti-HIV activity of C-peptide fusion inhibitors using a bivalent drug design approach.

We reported the design of fusion inhibitors with improved activity using a multivalent inhibitor design strategy. First, we chose C29 as the template sequence, which is a 29-mer peptide derived from HIV-1 gp41 CHR domain and has anti-HIV activity of IC50 118 nM in a cell-cell fusion assay. We optimized the crosslink sites and linkers of the template peptide.

Covalent fusion inhibitors targeting HIV-1 gp41 deep pocket.

Covalent inhibitors form covalent adducts with their target, thus permanently inhibiting a physiological process. Peptide fusion inhibitors, such as T20 (Fuzeon, enfuvirtide) and C34, interact with the N-terminal heptad repeat of human immunodeficiency virus type 1 (HIV-1) gp41 glycoprotein to form an inactive hetero six-helix bundle (6-HB) to prevent HIV-1 infection of host cells. A covalent strategy was applied to peptide fusion inhibitor design by introducing a thioester group into C34-like peptide.

Inter-chain acyl transfer reaction in a peptide six-helical bundle: a chemical method for regulating the interaction between peptides or proteins.

An inter-helical acyl transfer specifically occurred between the C-and N-peptides of HIV gp41 after assembly of the six-helical bundle (6HB), forming an inter-helical covalent bond that greatly enhanced 6HB stability. In the reaction, the C-peptide was modified as an acyl donor, and the N-peptide served as an acyl acceptor.