139115-90-5Relevant articles and documents
Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect
Xiao, Qiang,Bécar, Natalie A.,Brown, Nathaniel P.,Smith, Mason S.,Stern, Kimberlee L.,Draper, Steven R.E.,Thompson, Katherine P.,Price, Joshua L.
, p. 8933 - 8939 (2018)
Hydrocarbon stapling and PEGylation are distinct strategies for enhancing the conformational stability and/or pharmacokinetic properties of peptide and protein drugs. Here we combine these approaches by incorporating asparagine-linked O-allyl PEG oligomers at two positions within the β-sheet protein WW, followed by stapling of the PEGs via olefin metathesis. The impact of stapling two sites that are close in primary sequence is small relative to the impact of PEGylation alone and depends strongly on PEG length. In contrast, stapling of two PEGs that are far apart in primary sequence but close in tertiary structure provides substantially more stabilization, derived mostly from an entropic effect. Comparison of PEGylation + stapling vs. alkylation + stapling at the same positions in WW reveals that both approaches provide similar overall levels of conformational stability.
Redefining Protein Interfaces within Protein Single Crystals with DNA
Han, Zhenyu,Mirkin, Chad A.,Partridge, Benjamin E.,Winegar, Peter H.
, p. 8925 - 8934 (2021)
Proteins are exquisite nanoscale building blocks: molecularly pure, chemically addressable, and inherently selective for their evolved function. The organization of proteins into single crystals with high positional, orientational, and translational order results in materials where the location of every atom can be known. However, controlling the organization of proteins is challenging due to the myriad interactions that define protein interfaces within native single crystals. Recently, we discovered that introducing a single DNA-DNA interaction between protein surfaces leads to changes in the packing of proteins within single crystals and the protein-protein interactions (PPIs) that arise. However, modifying specific PPIs to effect deliberate changes to protein packing is an unmet challenge. In this work, we hypothesized that disrupting and replacing a highly conserved PPI with a DNA-DNA interaction would enable protein packing to be modulated by exploiting the programmability of the introduced oligonucleotides. Using concanavalin A (ConA) as a model protein, we circumvent potentially deleterious mutagenesis and exploit the selective binding of ConA toward mannose to noncovalently attach DNA to the protein surface. We show that DNA association eliminates the major PPI responsible for crystallization of native ConA, thereby allowing subtle changes to DNA design (length, complementarity, and attachment position) to program distinct changes to ConA packing, including the realization of three novel crystal structures and the deliberate expansion of ConA packing along a single crystallographic axis. These findings significantly enhance our understanding of how DNA can supersede native PPIs to program protein packing within ordered materials.
A convergent synthesis of heterocyclic dendrimers using the 1,3-dipolar cycloaddition reaction of organic azides and acetylenedicarboxylate esters
Van Wuytswinkel, Grete,Verheyde, Bert,Compernolle, Frans,Toppet, Suzanne,Dehaen, Wim
, p. 1337 - 1340 (2000)
The convergent synthesis of heterocyclic dendrimers using 1,3-dipolar cycloaddition reaction of organic azides and acetylenedicarboxylate esters was discussed. It was found that the second generation dibromofumarate was prepared from monomer and the first
Selectively Targeting and Differentiating Vancomycin-Resistant Staphylococcus aureus via Dual Synthetic Fluorescent Probes
Wang, Tsung-Shing Andrew,Chen, Pin-Lung,Chen, Yi-Chen Sarah,Hung, Hsuan-Min,Huang, Jhih-Yi
, p. 2584 - 2590 (2021)
Many Staphylococcus bacteria are pathogenic and harmful to humans. Noticeably, some Staphylococcus, including vancomycin-resistant S. aureus (VRSA), have become notoriously resistant to antibiotics and have spread rapidly, becoming threats to public health. Here, we designed a dual fluorescent probe scheme combining siderophores and antibiotics as the guiding units to selectively target VRSA and vancomycin-sensitive S. aureus (VSSA) in complex bacterial samples. Siderophore-mediated iron uptake is the key pathway by which S. aureus acquires iron in limited environments. Therefore, the siderophore-derivative probe could differentiate between S. aureus and other bacteria. Moreover, by fine-tuning the vancomycin-derivative probes, we could selectively target only VSSA, further differentiating VRSA and VSSA. Finally, by combining the siderophore-derivative probe and the vancomycin-derivative probe, we successfully targeted and differentiated between VRSA and VSSA in complicated bacterial mixtures.
Hypoxia-Responsive19F MRI Probes with Improved Redox Properties and Biocompatibility
Xie, Da,Kim, Seyong,Kohli, Vikraant,Banerjee, Arnab,Yu, Meng,Enriquez, José S.,Luci, Jeffrey J.,Que, Emily L.
, p. 6429 - 6437 (2017)
19F magnetic resonance imaging (MRI), an emerging modality in biomedical imaging, has shown promise for in vitro and in vivo preclinical studies. Here we present a series of fluorinated Cu(II)ATSM derivatives for potential use as19F magnetic resonance agents for sensing cellular hypoxia. The synthesized complexes feature a hypoxia-targeting Cu2+ coordination core, nine equivalent fluorine atoms connected via a variable-length poly(ethylene glycol) linker. Introduction of the fluorine moiety maintains the planar coordination geometry of the Cu2+ center, while the linker length modulates the Cu2+/+ reduction potential,19F NMR relaxation properties, and lipophilicity. In particular, the19F NMR relaxation properties were quantitatively evaluated by the Solomon-Bloembergen model, revealing a regular pattern of relaxation enhancement tuned by the distance between Cu2+ and F atoms. Finally, the potential utility of these complexes for sensing reductive environments was demonstrated using both19F MR phantom imaging and19F NMR, including experiments in intact live cells.
Synthesis and antifungal activities of N-glycosylated derivatives of Tunicyclin D, an antifungal octacyclopeptide
Zhao, Qingjie,Zou, Yan,Guo, Junxiang,Yu, Shichong,Chai, Xiaoyun,Hu, Honggang,Wu, Qiuye
, p. 7780 - 7787 (2014)
A series of glycosylated derivatives of Tunicyclin D were synthesized through a highly efficient and versatile synthetic method. The method is based on solid-phase peptide synthesis using 2-chlorotrityl resin as the solid-phase support and glycosyl amino acids as building blocks. Biological studies of the synthetic Tunicyclin D derivatives showed monosaccharide-containing compounds exhibit improved or similar antifungal activities, whereas the compounds carrying disaccharide glycans, showed much weaker antifungal activities.
Towards the simplification of protein synthesis: Iterative solid-supported ligations with concomitant purifications
Aucagne, Vincent,Valverde, Ibai E.,Marceau, Philippe,Galibert, Mathieu,Dendane, Nabil,Delmas, Agnès F.
, p. 11320 - 11324 (2012)
Please release me: A new linker for the temporary tagging of peptides at their N-terminus after solid-phase elongation, and its potential for capture/release purification is demonstrated. This concept is extended to a remarkably efficient self-purifying N-to-C iterative triazole ligation strategy, which is applied to the synthesis of a polypeptide having 160 residues, in a high purity without the need for chromatographic purification (see picture; orange blocks: peptide segments). Copyright
Snap-top nanocarriers
Ambrogio, Michael W.,Pecorelli, Travis A.,Patel, Kaushik,Khashab, Niveen M.,Trabolsi, Ali,Khatib, Hussam A.,Botros, Youssry Y.,Zink, Jeffrey I.,Stoddart, J. Fraser
, p. 3304 - 3307 (2010)
(Equation Presented). An approach to the design and fabrication of mechanized mesoporous silica nanoparticles is demonstrated at the proof of principle level. It relies on the reductive cleavage of disulfide bonds within an integrated nanosystem, wherein surface-bound rotaxanes incorporate disulfide bonds in their stalks,-which are encircled by cucurbit[6]uril or α-cyclodextrin rings, until reductive chemistry is performed, resulting in the snapping of the stalks of the rotaxanes, leading to cargo release from the inside of the nanoparticles.
A dansyl-derivatized phytic acid analogue as a fluorescent substrate for phytases: experimental and computational approach
Dussouy, Christophe,Dubreucq, Eric,Chemardin, Patrick,Perrier, Véronique,Abadie, Josiane,Quiquampoix, Hervé,Plassard, Claude,Behr, Jean-Bernard
supporting information, (2021/03/22)
A new myo-inositol pentakisphosphate was synthesized, which featured a dansyl group at position C-5. The fluorescent tag was removed from the inositol by a 6-atom spacer to prevent detrimental steric interactions in the catalytic site of phytases. The PEG linker was used in order to enhance hydrophilicity and biocompatibility of the new artificial substrate. Computational studies showed a favorable positioning in the catalytic site of phytases. Enzymatic assays demonstrated that the tethered myo-inositol was processed by two recombinant phytases Phy-A and Phy-C, classified respectively as acid and alkaline phytases, with similar rates of phosphate release compared to their natural substrate.
