Article
Multidisciplinary Sciences
Thomas F. Durand-Reville, Alita A. Miller, John P. O'Donnell, Xiaoyun Wu, Mark A. Sylvester, Satenig Guler, Ramkumar Iyer, Adam B. Shapiro, Nicole M. Carter, Camilo Velez-Vega, Samir H. Moussa, Sarah M. McLeod, April Chen, Angela M. Tanudra, Jing Zhang, Janelle Comita-Prevoir, Jan A. Romero, Hoan Huynh, Andrew D. Ferguson, Peter S. Horanyi, Stephen J. Mayclin, Henry S. Heine, George L. Drusano, Jason E. Cummings, Richard A. Slayden, Ruben A. Tommasi
Summary: The study presents a rational design strategy for developing new antibiotics to combat infections caused by drug-resistant Gram-negative pathogens. The inhibitors are able to overcome multiple mechanisms of resistance and show potential clinical efficacy against superbugs.
Review
Chemistry, Multidisciplinary
Xuefei Wang, Duan Ni, Yaqin Liu, Shaoyong Lu
Summary: This review summarizes drug design strategies for protein-protein interactions (PPIs) targeting, specifically focusing on the development of peptide-based PPI inhibitors. Examples targeting well-known PPI targets such as Bcl-2 family members, p53-MDM2, and APC-Asef are presented to illustrate detailed schemes for peptide-based PPI inhibitor development and optimization. The review provides an overview of recent advances in drug discovery targeting PPIs through peptides or peptidomimetics, offering insights into future therapeutic agent development for historically challenging PPI systems.
FRONTIERS IN CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Jie Zhong, Yuegui Guo, Shaoyong Lu, Kun Song, Ying Wang, Li Feng, Zhen Zheng, Qiufen Zhang, Jiacheng Wei, Peng Sang, Yan Shi, Jianfeng Cai, Guoqiang Chen, Chen-Ying Liu, Xiuyan Yang, Jian Zhang
Summary: This study identifies a best-in-class inhibitor for the protein-protein interaction crucial to colorectal cancer metastasis and develops a sensitivity-enhanced tracer for fluorescence polarization assays to accurately detect high-activity inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Weiping Lyu, Qihang Li, Yingming Wang, Chenxi Du, Feng Feng, Heng Chi, Yuan Li, Wenyuan Liu, Haopeng Sun
Summary: Cellular autophagy is an intracellular degradation pathway that maintains cell homeostasis, and dysfunctions in autophagy are closely related to various diseases. The protein-protein interaction between LC3 and p62 plays a critical role in autophagosome formation, yet research on inhibitors targeting this interaction is still lacking.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Anthony Marchand, Lucia Bonati, Sailan Shui, Leo Scheller, Pablo Gainza, Steiphane Rosset, Sandrine Georgeon, Li Tang, Bruno E. Correia
Summary: Protein-based therapeutics, such as monoclonal antibodies and cytokines, are important treatments for various diseases, but their wide application is often limited by toxicities and adverse effects. In this study, researchers have designed and applied small-molecule-controlled switchable protein therapeutics by utilizing an OFF-switch system. By optimizing the affinity between B-cell lymphoma 2 protein and a designed protein partner, the addition of a competing drug can efficiently disrupt the protein function in vitro and lead to fast clearance in vivo. This study provides a proof-of-concept for the controllable design of protein-based therapeutics by introducing a drug-induced OFF-switch.
ACS CHEMICAL BIOLOGY
(2023)
Review
Chemistry, Medicinal
Tiandi Ding, Ying Zhi, Weilin Xie, Qingqiang Yao, Bo Liu
Summary: Sphingosine kinases are lipid kinases that phosphorylate sphingosine to sphingosine-1-phosphate, playing a role in regulating biological processes; targeting their signaling pathway is a potential treatment strategy for various pathophysiological conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Gianni Chessari, Ian R. Hardcastle, Jong Sook Ahn, Burcu Anil, Elizabeth Anscombe, Ruth H. Bawn, Luke D. Bevan, Timothy J. Blackburn, Ildiko Buck, Celine Cano, Benoit Carbain, Juan Castro, Ben Cons, Sarah J. Cully, Jane A. Endicott, Lynsey Fazal, Bernard T. Golding, Roger J. Griffin, Karen Haggerty, Suzannah J. Harnor, Keisha Hearn, Stephen Hobson, Rhian S. Holvey, Steven Howard, Claire E. Jennings, Christopher N. Johnson, John Lunec, Duncan C. Miller, David R. Newell, Martin E. M. Noble, Judith Reeks, Charlotte H. Revill, Christiane Riedinger, Jeffrey D. St Denis, Emiliano Tamanini, Huw Thomas, Neil T. Thompson, Mladen Vinkovic, Stephen R. Wedge, Pamela A. Williams, Nicola E. Wilsher, Bian Zhang, Yan Zhao
Summary: In this study, novel isoindolinone-based MDM2 inhibitors were designed with rational structure guidance and showed potent inhibition of MDM2-p53 interaction, leading to cytostasis in an osteosarcoma xenograft model. These findings highlight the potential of targeting MDM2 in cancer therapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Carolina T. Orozco, Manuela Bersellini, Lorraine M. Irving, Wesley W. Howard, David Hargreaves, Paul W. A. Devine, Elise Siouve, Gareth J. Browne, Nicholas J. Bond, Jonathan J. Phillips, Peter Ravn, Sophie E. Jackson
Summary: This study investigated the mechanism of designing ideal affinity-based masks for antibodies. By using different masks with various properties, the researchers identified four critical factors and validated the binding sites on the antibody using HDX-MS and crystal structure analysis.
Review
Virology
Hortense Decool, Lorene Gonnin, Irina Gutsche, Christina Sizun, Jean-Francois Eleouet, Marie Galloux
Summary: Pneumoviruses, including pathogenic human and animal viruses such as hRSV and hMPV, are major causes of severe respiratory illnesses in young children and vulnerable populations. Transcription and replication of these viruses rely on specific cytoplasmic inclusions and interactions between viral polymerase and cofactors. Recent structural studies on viral proteins aim to aid in the development of new antivirals against these viruses.
Review
Biochemistry & Molecular Biology
Sailan Shui, Stephen Buckley, Leo Scheller, Bruno E. Correia
Summary: Small-molecule responsive protein switches are important tools for controlling cellular processes, and recent advances in computational protein design have led to the development of switches that can respond to a wider range of small-molecule inducers with more sophisticated mechanisms.
Article
Biochemical Research Methods
Anna Yudenko, Anastasia Smolentseva, Ivan Maslov, Oleg Semenov, Ivan M. Goncharov, Vera V. Nazarenko, Nina L. Maliar, Valentin Borshchevskiy, Valentin Gordeliy, Alina Remeeva, Ivan Gushchin
Summary: Protein-fragment complementation assays are commonly used to study protein-protein interactions. The development of CagFbFP, a small thermostable FbFP based on a LOV domain-containing protein, provides a split fluorescent reporter that can be used to investigate protein-protein interactions in anaerobic conditions without the need for exogenous fluorophores. This advancement in fluorescent protein technology may lead to further development of LOV and PAS domain-based fluorescent reporters and optogenetic tools.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Chemistry, Medicinal
Qiuyue Zhang, Xuexuan Wu, Jianrui Zhou, Lixiao Zhang, Xiaoli Xu, Lianshan Zhang, Qidong You, Lei Wang
Summary: The HSP90-CDC37 protein-protein interaction system is crucial for kinase maturation and targeting this interaction has emerged as a promising strategy for cancer therapy. By studying inhibitors, a key hydrophobic pocket was identified, leading to the design of an optimum compound DDO-5994 with improved binding affinity and antiproliferative activity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Takumi Yokoyama, Takehiro Ando, Yukio Takamori, Daisuke Fuji, Masashi Sato, Santhana Vedi, Mizuki Yamamoto, Takashi Kawakami
Summary: This study reports a novel linker for SELEX of mRNA-displayed unnatural peptides, forming thioethers through intramolecular reactions.
CHEMICAL COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Kavita Bhagat, Jatinder V. Singh, Piyusha P. Pagare, Nitish Kumar, Anchal Sharma, Gurinder Kaur, Nihar Kinarivala, Srinivasa Gandu, Harbinder Singh, Sahil Sharma, Preet Mohinder S. Bedi
Summary: GABA is crucial in the central nervous system, and drugs targeting GABA receptors and transporters show promise in treating neurological disorders associated with decreased GABA activity.
MOLECULAR DIVERSITY
(2021)
Review
Chemistry, Multidisciplinary
Xinyu Wang, Shengnan Zhang, Jicong Zhang, Yaomin Wang, Xiaoyu Jiang, Youqi Tao, Dan Li, Chao Zhong, Cong Liu
Summary: This review provides a comprehensive overview of the design principles for functional amyloid fibrillar assemblies from an engineering perspective and through the lens of structural insights. The article introduces the fundamental structural configurations and functions of amyloid assemblies, and then focuses on two prevalent strategies for the design of functional amyloid fibrillar assemblies. Characterization techniques contribute to unveiling the structural polymorphism of amyloid fibrils and clarifying the regulation mechanisms of assembly and disassembly. The integration of structural tunability, synthetic biology, and artificial intelligence may lead to a new trend in functional amyloid design.
CHEMICAL SOCIETY REVIEWS
(2023)