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.