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

被引：14

作者：

Cheng, CT ^{[1
]}

Lo, V ^{[1
]}

Chen, J ^{[1
]}

Chen, WC ^{[1
]}

Lin, CY ^{[1
]}

Lin, HC ^{[1
]}

Yang, CH ^{[1
]}

Sheh, L ^{[1
]}

机构：

[1] Tunghai Univ, Dept Chem, Taichung 407, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2001年 / 9卷 / 06期

关键词：

D O I：

10.1016/S0968-0896(01)00043-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 10(3) M-1, whereas those of cyclic peptide 7b and linear Lys-Trp-Lys are 1.9 x 10(4) M-1 and 9.5 x 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 phi X174 DNA. with nicking rate of 50.7 and 75.6pM min(-1) at 65 degreesC, 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 degreesC, the DNA nicking rate of cyclic peptide 7b exceeded that of linear Lys-Trp-Lys. The addition of 1 muM 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. (C) 2001 Elsevier Science Ltd. Ail rights reserved.

引用

页码：1493 / 1498

页数：6

共 16 条

[1] INTERACTIONS OF AROMATIC RESIDUES OF PROTEINS WITH NUCLEIC-ACIDS - FLUORESCENCE STUDIES OF BINDING OF OLIGOPEPTIDES CONTAINING TRYPTOPHAN AND TYROSINE RESIDUES TO POLYNUCLEOTIDES [J].