The molecular host cucurbit[7]uril forms an extremely stable inclusion complex with the dicationic ferrocene derivative bis(trimethylammoniomethyl)ferrocene in aqueous solution. The equilibrium association constant for this host-guest pair is 3 x 10(15) M(-1) (K(d) = 3 x 10(-16) M), equivalent to that exhibited by the avidin-biotin pair. Although purely synthetic systems with larger association constants have been reported, the present one is unique because it does not rely on polyvalency. Instead, it achieves its extreme affinity by overcoming the compensatory enthalpy-entropy relationship usually observed in supramolecular complexes. Its disproportionately low entropic cost is traced to extensive host desolvation and to the rigidity of both the host and the guest.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410071 | PMC |
http://dx.doi.org/10.1073/pnas.0706407105 | DOI Listing |
J Cell Biol
March 2025
Department of Biological Sciences, Laboratory of Cell Biology and Biochemistry, Tokyo Metropolitan University, Tokyo, Japan.
The accumulation of defective polypeptides in cells is a major cause of various diseases. However, probing defective proteins is difficult because no currently available method can retrieve unstable defective translational products in a soluble state. To overcome this issue, there is a need for a molecular device specific to structurally defective polypeptides.
View Article and Find Full Text PDFDynein-1 is a microtubule motor responsible for the transport of cytoplasmic cargoes. Activation of motility requires it first overcome an autoinhibited state prior to its assembly with dynactin and a cargo adaptor. Studies suggest that Lis1 may relieve dynein's autoinhibited state.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
View Article and Find Full Text PDFSci Rep
January 2025
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Antibody-drug conjugates (ADCs) are an emerging strategy in cancer therapy, enhancing precision and efficacy by linking targeted antibodies to potent cytotoxic agents. This study introduces a novel ADC that combines ribonuclease A (RNase A) with cetuximab (Cet), an anti-EGFR monoclonal antibody, through a polyethylene glycol (PEG) linker (RN-PEG-Cet), aimed to induce apoptosis in KRAS mutant colorectal cancer (CRC) via a ROS-mediated pathway. RN-PEG-Cet was successfully synthesized and characterized for its physicochemical properties, retaining full enzymatic activity in RNA degradation and high binding affinity to EGFR.
View Article and Find Full Text PDFParasitol Res
January 2025
Department of Biology, Faculty of Science, Marmara University, Goztepe, 34722, Istanbul, Türkiye.
Babesia bigemina is an apicomplexan parasite responsible for causing "Texas fever" in bovines. Current treatments for bovine babesiosis are hindered by several limitations, including toxicity, insufficient efficacy in eliminating the parasite, and the potential for resistance development. A promising approach to overcome these challenges is the identification of compounds that specifically target essential metabolic pathways unique to the parasite.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!