Spectroscopic and SEM evidences for G4-DNA binding by a synthetic alkyne-containing amino acid with anticancer activity

Herein, we present a spectroscopic (CD and UV) and SEM study of a phenylalanine derivative carrying a terminal alkyne moiety and indicated by us CF3IIIPhe, with particular attention to its interaction with Cu(II) cation and some biological macromolecules, as well as a preliminary evaluation of its effect on cancerous cells. CD spectroscopy evidenced the ability of CF3IIIPhe to interact with tel26 and c-myc, two quadruplex DNA (G4 DNA) models explored in this study. Other CD and UV studies revealed the ability of the unnatural amino acid to form aggregates in aqueous solution, to bind Cu(II) cation, and to interact with bovine serum albumin (BSA). Cellular studies demonstrated CF3IIIPhe antiproliferative activity on PC3 cells. Its ability to bind telomeric DNA was verified with tel26 by CD investigation and SEM analysis, that revealed a noteworthy change in DNA morphology (mainly based on nanosphere structures) by CF3IIIPhe, confirming its G4-DNA binding ability already evidenced by spectroscopy. [Display omitted] •CF3IIIPhe is a novel aromatic amino acid synthesized via Ni (II)-complex intermediates.•Copper ion binding with the formation of CuL2 complexes•CD and molecular docking studies on the interaction of CF3IIIPhe with BSA•Spectroscopic and SEM studies with quadruplex (G4) forming telomeric and c-myc DNA sequences•Antiproliferative activity of CF3IIIPhe against prostate cancer cells