Synthesis and DNA nicking studies of a novel cyclic peptide: Cyclo[Lys-Trp-Lys-Ahx-]

Two novel cyclic tetrapeptides: cyclo[Lys-Tyr-Lys-Ahx-] 7a and cyclo[Lys-Trp-Lys-Ahx-] 7b were synthesized by coupling protected amino acid in solution and the subsequent cyclization effected by the pentafluorophenyl ester method as described in previous papers. These cyclic peptides were designed a...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2001-06, Vol.9 (6), p.1493-1498
Main Authors: Cheng, Chong-Teh, Lo, Vivian, Chen, Johnson, Chen, Wan-Chi, Lin, Cheng-Yun, Lin, He-Ching, Yang, Chia-Hung, Sheh, Leung
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Biological and medical sciences
DNA - chemistry
DNA - metabolism
DNA - radiation effects
Dna, deoxyribonucleoproteins
Electrophoresis, Agar Gel
Fundamental and applied biological sciences. Psychology
Nucleic acids
Oligopeptides - chemistry
Peptides, Cyclic - chemistry
Peptides, Cyclic - metabolism
Ultraviolet Rays
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Summary:Two novel cyclic tetrapeptides: cyclo[Lys-Tyr-Lys-Ahx-] 7a and cyclo[Lys-Trp-Lys-Ahx-] 7b were synthesized by coupling protected amino acid in solution and the subsequent cyclization effected by the pentafluorophenyl ester method as described in previous papers. These cyclic peptides were designed and synthesized to study their interaction with DNA, based on previous reports that linear peptides Lys-Tyr-Lys and Lys-Trp-Lys could bind to various forms of DNA and cleaved supercoiled DNA at apurinic sites. Ethidium bromide displacement assay showed that the apparent DNA binding constant of linear Lys-Tyr-Lys and cyclic peptide 7a are far below 1×10 3 M −1, whereas those of cyclic peptide 7b and linear Lys-Trp-Lys are 1.9×10 4 M −1 and 9.5×10 3 M −1, respectively. Kinetic studies using agarose gel electrophoresis showed that cyclic peptide 7b and Lys-Trp-Lys possessed DNA nicking activity on natural supercoiled φX174 DNA with nicking rate of 50.7 and 75.6 pM min −1 at 65 °C, respectively, whereas cyclic peptide 7a and linear Lys-Tyr-Lys were devoid of the corresponding activity. The DNA nicking rate increased significantly with increase in reaction temperature. At reaction temperatures lower than 65 °C , the DNA nicking rate of cyclic peptide 7b exceeded that of linear Lys-Trp-Lys. The addition of 1 μM ferrous ion did not give significant enhancement effect on the DNA nicking rate by the peptides. UV irradiation gave a marked rate enhancement on the DNA nicking rate of linear Lys-Trp-Lys and a moderate enhancement on the DNA nicking rate of cyclic peptide 7b. A synthetic cyclic peptide: cyclo[Lys-Trp-Lys-Ahx-] was found to have DNA nicking properties on natural supercoiled φX174 DNA whereas cyclo[Lys-Tyr-Lys-Ahx-] and Lys-Tyr-Lys did not posses similar activity. The DNA nicking rate increased with increase in temperature. At reaction temperatures lower than 60 °C, the DNA nicking rate of cyclo[Lys-Trp-Lys-Ahx-] exceeded that of linear Lys-Trp-Lys.
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(01)00043-8