Search

Cyclic peptides has become an attractive modality for drug development due to their excellent binding affinity, target selectivity and low toxicity, however significant activity difference between the synthetic and natural cyclic peptides such as Phakillestatins has puzzled chemists for years. In an effort to explore the bioactive secondary structures, three pairs of cyclic Phakellistatin 6 analogs with special constrained stereo-features were prepared by regioselectively controlled intramolecular photoinduced single electron transfer (SET) reactions in this paper. The spatial configurationally features were systematically investigated by ECD and NMR, together with detailed structural analysis based on theoretical calculations, which showed that conventional turns rather than irregular γ-/β-turn secondary structures played important roles for the antitumor activities. We also presented the in vitro bioactive assay, liposomal leakage assays and electron microscopy analyses, which indicated the prepared cyclopeptide analogs excellent antitumor activities, most showing greater growth inhibitory effects than that of the famous anticancer agent paclitaxel. Image 1 • Novel Phakellistatin 6 analogs were stereoselectively synthesized by photoinduced cyclization. • Their absolute configurations were determined by experimental and theoretical ECD spectra. • The spatial configurationally features affecting the antitumor activities were elucidated in detail. [ABSTRACT FROM AUTHOR]