A single-chain variable fragment-anticancer lytic peptide (scFv-ACLP) fusion protein for targeted cancer treatment.

Antibody-directed drugs for targeted cancer treatment have become a hot topic in new anticancer drug development; however, antibody-fused therapeutic peptides were rarely documented. Herein, we designed a fusion protein with a cetuximab-derived single-chain variable fragment targeting epidermal growth factor receptor (anti-EGFR scFv) and the anticancer lytic peptide (ACLP) ZXR2, connected by a linker (G S) and MMP2 cleavage site. The anti-EGFR scFv-ZXR2 recombinant protein showed specific anticancer activity on EGFR-overexpressed cancer cell lines in a concentration- and time-dependent manner, as it can bind to EGFR on cancer cell surfaces.

Phase separation of p53 induced by its unstructured basic region and prevented by oncogenic mutations in tetramerization domain.

Liquid-liquid phase separation (LLPS) drives the formation of extensive membrane-less compartments to regulate various cellular biological activities both physiologically and pathologically. It has been widely accepted that LLPS is closely related to amyloid diseases and increasing reports have linked this phenomenon to cancers. Mutations of tumor suppressor protein p53 exist in more than half of malignant tumors, making the protein vitally important in cancer research.

Computer-Aided Design of Lasso-like Self-Assembling Anticancer Peptides with Multiple Functions for Targeted Self-Delivery and Cancer Treatments.

Anticancer peptides are promising drug candidates for cancer treatment, but the short circulation time and low delivery efficiency limit their clinical applications. Herein, we designed several lasso-like self-assembling anticancer peptides (LASAPs) integrated with multiple functions by a computer-aided approach. Among these LASAPs, LASAP1 (CRGDKGPDCGKAFRRFLGALFKALSHLL, 1-9 disulfide bond) was determined to be superior to the others because it can self-assemble into homogeneous nanoparticles and exhibits improved stability in serum.

The SGYS motif of TAF15 prion-like domain is critical to amyloid fibril formation.

Misfolding of TATA-box binding protein-associated factor 15 (TAF15) may cause neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Some mutations of prion-like domain (PrLD) have been detected in patients with sporadic ALS, suggesting the importance of TAF15-PrLD in ALS pathogenesis. Herein, combining experiments and molecular dynamics (MD) simulations, we investigated the influences of several TAF15-PrLD mutations on the amyloid fibril formation of TAF15-PrLD-extracted peptide segments, and identified an essential β-amyloid-forming segment from TAF15-PrLD.