tLyp-1: A peptide suitable to target NRP-1 receptor.

Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity. It is mediated by endocytosis via C-end rule (CendR) internalization pathway. The aim of this study is to evaluate the importance of each amino acid in the tLyp-1 sequence through alanine-scanning (Ala-scan) technique, during which each of the amino acid in the sequence was systematically replaced by alanine to produce 7 different analogues. In silico approach through molecular docking and molecular dynamics are employed to understand the interaction between the peptide and its analogues with the NRP-1 receptor, followed by in vitro ligand binding assay study. The C-terminal Arg is crucial in the interaction of tLyp-1 with NRP-1 receptor. Substituting this residue dramatically reduces the affinity of this peptide which is clearly seen in this study. Lys-4 is also important in the interaction, which is confirmed via the in vitro study and the MM-PBSA analysis. The finding in this study supports the CendR, in which the presence of R/K-XX-R/K motif is essential in the binding of a ligand with NRP-1 receptor. This presented work will serve as a guide in the future work pertaining the development of active targeting agent towards NRP-1 receptor.

Synthesis, Characterization and Antibacterial Application of Copolymers Based on N,N-Dimethyl Acrylamide and Acrylic Acid.

Hydrogel copolymers based on N,N-dimethyl acrylamide (DMA) and acrylic acid (AAc) were synthesized using a solution polymerization technique with different monomer ratios and ammonium persulfate as an initiator. This paper investigates the thermal stability, physical and chemical properties of the hydrogel copolymer. Testing includes Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and elemental analysis (CHNS). The copolymer composition was determined by elemental analysis, and the reactivity ratios of monomers were calculated through linearization methods such as Fineman-Ross (FR), inverted Fineman-Ross (IFR), Kelen-Tudos (KT) and Mayo-Lewis (ML). Good agreement was observed between the results of all four methods. The ratio of r1 and r2 were 0.38 (r1) and 1.45 (r2) (FR), 0.38 (r1) and 1.46 (r2) (IFR), 0.38 (r1) and 1.43 (r2) (KT), and 0.38 (r1) and 1.45 (r2) (ML). Hydrogel copolymers exhibited good thermal stability, and SEM showed three-dimensional porous structures. Antibiotic-free and antibiotic-loaded hydrogels demonstrated antimicrobial properties against both Gram-positive and Gram-negative bacteria. As the ratio of DMA in hydrogel copolymer increased, the activity of copolymer against bacteria enhanced. The results indicated that these hydrogels have the potential to be used as antibacterial materials.