Zinc(II) complexes of Pro-Gly and Pro-Leu dipeptides: synthesis, characterization, in vitro DNA binding and cleavage studies.

Abstract

Dipeptide (Pro-Gly and Pro-Leu) Zinc(II) complexes 1 and 2 were designed and synthesized for potential use as cancer chemotherapeutic agents. In order to augment the DNA recognition of metallonuclease activity, zinc metal ion was tethered to peptide motif to carry out DNA site specific hydrolytic cleavage. The structural formulation of the complexes 1 and 2 was done by elemental analysis, spectroscopic methods (IR, NMR, electronic) and molar conductance measurements. Their in vitro DNA binding profile was investigated by UV-vis titrations, fluorescence titrations and circular dichroism which revealed that these complexes bind to CT DNA by electrostatic interactions via groove binding mode. Zn(II) Pro-Gly complex 1 showed greater binding affinity to CT DNA as compared to the Zn(II) Pro-Leu complex 2 due to steric constraints in the latter. The supercoiled pBR322 DNA cleavage activity of complex 1, ascertained by gel electrophoresis demonstrated efficient DNA cleaving ability via hydrolytic mechanistic pathway. Further, the molecular docking studies confirmed that complex 1 bind to the minor groove of DNA having AT-rich sequences with relative binding energy of -196.72kJmol(-1).

• Authors: Shazia Parveen, Farukh Arjmand, D K Mohapatra
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 126 Pg. 78-86 (Sep 05 2013) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 23911763 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Dipeptides
• Organometallic Compounds
• prolylglycine
• prolylleucine
• DNA
• Ethidium
• Zinc

Topics

• Animals
• Cattle
• Chemistry Techniques, Synthetic
• DNA (chemistry, metabolism)
• DNA Cleavage (drug effects)
• Dipeptides (chemistry)
• Ethidium (chemistry)
• Hydrolysis
• Models, Molecular
• Nucleic Acid Conformation
• Organometallic Compounds (chemical synthesis, chemistry, metabolism, pharmacology)
• Zinc (chemistry)