title: De Novo Design and Synthesis of a γ-Turn Peptidomimetic Scaffold and Its Application as JNK3 Allosteric Ligand.
abstract: As a way to develop a neuroprotective agent for the JNK3-JIP1-binding site, peptidomimetics of JIP-1 as JNK3 allosteric regulators have been examined. The study consisted of in silico scaffold hopping, molecular docking, solution and solid-phase peptide syntheses, and Kd measurements using surface plasmon resonance. As a peptidomimetic of JIP1, heptamer mimetic 16 (Kd =2.72 μm) displayed a higher affinity than decamer JIP1 (Kd =23.6 μm). The high affinity of 16 implies that the characteristic γ-turn mimetic structure, ""Φ-X-Φ" hydrophobic motif in 16, increased its affinity toward the JIP-site of JNK3.
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do, 426-791, Korea.|Department of Pharmacy, College of Pharmacy & Gachon Institute of Pharmaceutical Science, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon, 406-840, Korea.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do, 426-791, Korea.
authors.forename: Junghun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do, 426-791, Korea. jhah@hanyang.ac.kr.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D008024:Ligands; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D057786:Peptidomimetics; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C520352:JNK-interacting protein 1 (153-163); D008024:Ligands; D010446:Peptide Fragments; D057786:Peptidomimetics; D047428:Protein Kinase Inhibitors; D048057:Mitogen-Activated Protein Kinase 10
keywords: JNK3; allosteric; gamma turn; kinase inhibitors; peptidomimetics; scaffold hopping