Synthesis, characterization of Cu(II) and Zn(II) complexes of proline-glycine and proline-leucine tetrapeptides: In vitro DNA binding and cleavage studies

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• 作者：Farukh Arjmand^a ; ^{farukh_arjmand@yahoo.co.in} ; Shazia Parveen^a ; D.K. Mohapatra^b
• 关键词：UV&ndash ; Vis ; ultraviolet&ndash ; visible ; CT DNA ; calf thymus DNA ; 5&prime ; -GMP ; guanosine 5&prime ; -monophosphate ; 5&prime ; -TMP ; thymidine 5&prime ; -monophosphate ; HOBT ; N-hydroxybenzotriazole ; EDCI ; 1-ethyl-3-(3dimethylaminopropyl)carbodiimide hydrochlorid
• 出版年：2012
• 期刊代码：40_00201693
• 类别：ch
• 出版时间：15 June, 2012
• 卷：388
• 期：Complete
• 页码：1-10
• 文件大小：856 K

摘要

New Cu(II) and Zn(II)-based peptide solid complexes ng class="boldFont">1ng>-ng class="boldFont">4ng> were designed by de novo synthetic strategy from tetrapeptide ligands, Pro-Gly-Pro-Gly, ng class="boldFont">Lng>¹/Pro-Leu-Pro-Leu, ng class="boldFont">Lng>² and thoroughly characterized by various spectroscopic techniques. To confirm the stability of peptide complexes in solution, solution stability studies of ng class="boldFont">1ng> and ng class="boldFont">3ng> over a pH range 2-12 were carried out which revealed no change in absorption or intensity of bands. In vitro DNA binding studies employing various optical techniques were carried out to examine the propensity of complexes towards CT DNA. The results of corroborative experiments reveal that the complexes avidly bind to CT DNA via groove binding, with highest K_b values for ng class="boldFont">1ng> indicative of strong binding propensity as compared to ligands and ng class="boldFont">2ng>-ng class="boldFont">4ng>. To compare the binding affinity for nucleotides, UV-Vis titrations of ng class="boldFont">1ng> and ng class="boldFont">2ng> with 5鈥?GMP and 5鈥?TMP were carried out; further validated by ¹H and ³¹P NMR. The supercoiled pBR322 DNA nuclease activity ng class="boldFont">1ng> and ng class="boldFont">2ng>, demonstrated that both the complexes were capable of cleaving DNA but with striking differences in their nuclease activity; Cu(II) complex cleaved DNA through oxidative cleavage while Zn(II) complex followed hydrolytic cleavage pathway.