Selection of Inhibitory Peptides for Aurora-A Kinase from a Phage-displayed Library of Helix-Loop-Helix Peptides
Combinatorial peptide libraries have been broadly recognized as useful resources for screening bioactive ligands that bind to receptors and enzymes. However, the identified peptides generally possess considerable conformational flexibility, so they show provide no 3D information of the pharmacophores in the interaction between the peptides and the targeted proteins. These facts have accelerated attempts to construct conformationally restricted peptide libraries by grafting randomized amino acid sequences onto a rigid scaffold derived from natural proteins, or incorporating them into stable secondary structural motifs.1 Previously, as a library scaffold, we proposed a de novo designed helix-loophelix motif, which is characterized by two a-helices connected by a loop, and constructed a phagedisplayed peptide library of the -helix region to screen against a cytokine (G-CSF) receptor or a ganglioside (GM1).2-4 In the present work, we have constructed a intramolecular antiparallei helix-loophelix peptide YT1 (AELAALEAELAALE-G7-KLAALKAKLAALKA) as a library scaffold (Figure 1), and have screened against Aurora-A, which is a member of the Aurora family of serine/threonine protein kinases. Aurora-A is critical for the proper regulation of mitosis and is often targeted in anti-cancer drug discovery, this report is the first example of de novo peptides recognizing Aurora-A.
Zhengmao Ye Daisuke Fujiwara Masaki Gouda Koichi Yokota Takeshi Tsumuraya Ikuo Fujii
Department of Biological Science,Graduate School of Science,Osaka Prefecture University,1-1,Gakuen-c Research and Development Department,Carna Bioscience Inc.,BMA 3F 1-5-5 Minatojima-Minamimachi,Chuo-k
国际会议
The Eleventh China-Japan-Korea Joint Symposium on Enzyme Engineering(第十一届中日韩酶工程学术研讨会)
成都
英文
92-94
2010-11-05（万方平台首次上网日期，不代表论文的发表时间）