Spectroscopic studies on noncovalent binding of nicotinamide-modified BRCA1 (856-871) analogs to calf thymus DNA.

Various peptide drugs have entered the market with the development of molecular biology. Peptide drugs are used for treat diseases such as diabetes, breast cancer, and HIV infection. In this study, three nicotinamide-modified peptides were synthesized by modifying the N-terminus of BRCA1 (856-871, Y856R, K862Y, R866W) peptide with three nicotinic acid derivatives using solid-phase peptide synthesis. The results of calf thymus DNA (ctDNA) binding activity indicated that binding constants of BRCA1 (856-871, Y856R, K862Y, R866W) (P0) and three nicotinamide-modified peptides (P1, P2, and P3) to ctDNA were 1.89 × 103, 2.97 × 104, 7.61 × 104, and 8.09 × 104 L·mol-1, respectively. The binding affinity of the modified peptides was superior to that of BRCA1 (856-871, Y856R, K862Y, R866W). ΔHθ < 0 and ΔSθ < 0 indicated that van der Waals force and hydrogen bond contributed most to peptide-ctDNA binding. Results obtained by Circular dichroism (CD) indicated that peptide binding interaction led to conformational changes in ctDNA. Ultraviolet-visible (UV) spectroscopy, ethidium bromide (EB) competition experiments, DNA melting experiments, and viscosity measurements verified that peptides interacted with ctDNA via groove binding. Ionic strength experiments manifested that electrostatic binding was also involved in peptide-ctDNA binding.

Interaction of bifunctional peptide-carbazole complexes with DNA and antimicrobial activity.

Two peptide-carbazole conjugates, CTAT and CNLS, were designed and synthesized using carbazole Schiff base to modify the cell membrane penetrating peptide TAT (47-57) and the nuclear localization peptide NLS at the N terminus. The interaction with ctDNA was investigated by multispectral and agarose gel electrophoresis. And the effects of CNLS and CTAT on the G-quadruplex structure were explored by circular dichroism titration experiments. The results show that both CTAT and CNLS interact with ctDNA in a minor groove binding manner. Both conjugates bind more tightly to DNA than the individual substances CIBA, TAT and NLS. In addition, CTAT and CNLS are capable of unfolding parallel G-quadruplex structures and are potential G-quadruplex unfolding agents. Finally, broth microdilution was performed to test the antimicrobial activity of the peptides. The results showed that CTAT and CNLS had a 4-fold increase in antimicrobial activity compared with the parent peptides TAT and NLS. They could exert antimicrobial activity by disrupting the integrity of cell membrane bilayer and binding to DNA, and could be used as novel antimicrobial peptides for the development of novel antimicrobial antibiotics.

YAFAF-Based Hydrogel: Characterization, Mechanism, and Factors Influencing Micro-organization.

The YAFAF-based hydrogel was a three-dimensional network cross-linked by grooved fiber bundles. The fiber bundles were formed by entanglement of fibrils with a diameter of 2 nm, and the surface of the fibrils also presented grooves. Spectroscopic analysis revealed that the main secondary structures were ß-sheets and ß-turns, which led to the grooved feature of fibrils. In comparison of the nuclear magnetic resonance spectra of peptide solutions at 313 and 277 K, the nuclear Overhauser effects can be clearly observed, indicating that hydrogen-bondings and π-π stacking interactions play important roles in self-assembly. The micro-organization of the self-assemblies was affected by the ratio of solvents (xA) remarkably. Unexpectedly, xA of 0.05 produced hollow spherical aggregates. The result of these investigations on the mechanism and organization of the YAFAF-based hydrogel can contribute to the development of strategies using hydrogels in the food industry.

Antimicrobial Peptides with Rigid Linkers against Gram-Negative Bacteria by Targeting Lipopolysaccharide.

A series of hybrid peptides were designed by connecting an antimicrobial peptide Ce(1-8) with a lipopolysaccharide (LPS)-targeting peptide Lf(28-34) via different linkers. Antimicrobial experimental results indicated that linkers play an essential role in the anti-Gram-negative bacterial activity of the hybrid peptides. Among these hybrid peptides, peptide CL5 with dipeptide rigid linker LP exhibited excellent activity and selectivity against Gram-negative bacteria. The minimum inhibitory concentrations of CL5 against the tested Gram-negative bacteria were 4-32 µM, while the toxicity toward HEK-293 cells was relatively low. It was found that the interactions of the peptides with LPS were crucial for peptide activity against Gram-negative bacteria. Antimicrobial mechanistic studies showed that peptide CL5 contributed to the death of Gram-negative bacterial cells by disrupting the integrity of the bacterial membranes. This study revealed the importance of linker selection in the design of hybrid peptides and provides the basis for the further development of antimicrobial peptides.