For last few decades, the active site cleft and substrate-binding site of enzymes as well as ligand-binding site of the receptors have served as the main pharmacological space for drug discovery. However, rapid accumulation of proteome and protein network analysis data has opened a new therapeutic space that is the interface between the interacting proteins. Due to the complexity of the interaction modes and the numbers of the participating components, it is still challenging to identify the chemicals that can accurately control the protein-protein interactions at desire. Nonetheless, the number of chemical drugs and candidates working at the interface of the interacting proteins are rapidly increasing. This review addresses the current case studies and state-of-the-arts in the development of small chemical modulators controlling the interactions of the proteins that have pathological implications in various human diseases such as cancer, immune disorders, neurodegenerative and infectious diseases.
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http://dx.doi.org/10.1016/j.bmc.2011.12.016 | DOI Listing |
Commun Chem
December 2024
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
The PepT transporter mediates the transport of peptides across biological membranes. Despite advancements in structural biology, including cryogenic electron microscopy structures resolving PepT in different states, the molecular basis of peptide recognition and transport by PepT is not fully elucidated. In this study, we used molecular dynamics simulations, Markov State Models (MSMs), and Transition Path Theory (TPT) to investigate the transport mechanism of an alanine-alanine peptide (Ala-Ala) through the PepT transporter.
View Article and Find Full Text PDFLight Sci Appl
January 2025
Center for Nanoscience and Technology, Istituto Italiano di Tecnologia, Milano, 20134, Italy.
We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
University of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, NDM Research Building, Roosevelt Drive, OX3 7FZ, Oxford, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.
Choline kinase alpha (CHKA) is a central mediator of cell metabolism linked to cancer and immune regulation. Cellular and clinical evaluation of CHKA has been hampered by challenges in the development of drug-like choline kinase inhibitors. Here, we identify CHKA as an unexpected off-target of histone methyltransferase inhibitors using an integrated phenomic approach.
View Article and Find Full Text PDFDev Neurobiol
January 2025
Neuropharmacology Research Laboratory, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.
Owing to the high prevalence of gastrointestinal dysfunction in patients, the gut-brain axis is considered to play a vital role in neurodevelopment diseases. Recent pieces of evidence have pointed to the usage of antibiotics at an early developmental stage to be a causative factor in autism due to its ability to induce critical changes in the gut microbiota. The purpose of the study is to determine the neuroprotective effect of capric acid (CA) on autism in antibiotic-induced gut dysbiosis in rodents.
View Article and Find Full Text PDFBiochemistry
December 2024
Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
(Mtb) is a leading cause of death, with an escalating global occurrence of drug-resistant infections that are partially attributed to cell wall mycolic acids derived from type II fatty acid biosynthesis (FAS-II). Here, the central acyl carrier protein, AcpM, contributes to the regulation of complex and specific protein-protein interactions (PPIs), though the orchestration of these events remain largely unresolved due to unique features of AcpM. Limitations include complexities in generating modified AcpM in a single state.
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