%0 Journal Article
%T Use of a Designed Peptide Library to Screen for Binders to a Particular DNA G-Quadruplex Sequence
%A Keita Kobayashi
%A Noriko Matsui
%A Kenji Usui
%J Journal of Nucleic Acids
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/572873
%X We demonstrated a method to screen for binders to a particular G-quadruplex sequence using easily designed short peptides consisting of naturally occurring amino acids and mining of binding data using statistical methods such as hierarchical clustering analysis (HCA). Despite the small size of the library used in this study, candidates of specific binders were identified. In addition, a selected peptide stabilized the G-quadruplex structure of a DNA oligonucleotide derived from the promoter region of the protooncogene c-MYC. This study illustrates how a peptide library can be designed and presents a screening guideline for construction of G-quadruplex binders. Such G-quadruplex peptide binders could be functionally modified to enable switching, cellular penetration, and organelle-targeting for cell and tissue engineering. 1. Introduction Research over the last few decades has revealed that some DNA and RNA secondary structures modulate a variety of cellular events. One secondary structure in particular, the G-quadruplex [1] regulates cellular events such as transcription, translation, pre-RNA splicing, and telomerase elongation, all of which play roles in various serious diseases and cellular aging [2¨C6]. Systems capable of controlling DNA and RNA G-quadruplex structures would therefore be useful for the modulation of various cellular events for the purpose of producing biological effects. Because of their biological importance, many G-quadruplex-targeting ligands [7, 8] have been described, including phthalocyanine derivatives [9], porphyrin derivatives [10], and others [11¨C14]. However, the next generation of binders should have more G-quadruplex sequence specificity, higher inducing or collapsing ability of the structure, and a greater degree of functionality including binding on-off switching, cellular penetration, and the ability to target organelles. De novo designed peptides (peptides not derived from domains of binding proteins) are promising next generation G-quadruplex binding candidates because of the following advantages they offer: (i) peptides are easier to design and synthesize than antibodies or recombinant proteins; (ii) they can mimic protein-G-quadruplex interactions; (iii) analyses based on peptide libraries can be used to elucidate binding properties of DNAs; (iv) in addition to naturally occurring amino acids, various functional moieties (e.g., artificial amino acids) can be employed as building blocks in designed peptides; (v) because certain peptide sequences may exhibit transmembrane or hormonal properties, combining peptides
%U http://www.hindawi.com/journals/jna/2011/572873/