This paper reports on the cell uptake and trafficking properties of a series of non‐covalent polymer–drug conjugates. These nanomedicines are composed of a poly(N‐(2‐hydroxypropyl)methacrylamide) backbone functionalized with multiple copies of a drug. The drug moieties are attached to the polymer via a non‐covalent, so called coiled coil motif, which is formed by heterodimerization of two complementary peptide strands, one of which is attached to the polymer carrier and the other to the drug. Cytotoxicity and FACS experiments, which were carried out with model anticancer drug or fluorophore conjugates, provided insight into the cell uptake and trafficking behavior of these conjugates.
Conjugated oligomers with a trifluoromethylpyridazine unit have been synthesized by Suzuki crosscoupling reaction. These oligomers could be used as building block for construction of supramolecules or as liquid crystals when they are substituted by long chain alkoxy groups. 相似文献
Treatment of the acyclic zwitterionic pentacoordinate silicate F(3)MeSiCH(2)NMe(2)H with 1 molar equiv of Me(3)SiOC(6)H(4)OSiMe(3), Me(3)SiOCH(2)C(O)OSiMe(3), Me(3)SiOC(Ph)=NOSiMe(3), or Me(3)SiOC(O)C(O)OSiMe(3) (solvent CH(3)CN, room temperature) yielded the respective monocyclic zwitterionic pentacoordinate silicates (11a), (12a), (13a), and (14a), along with 2 molar equiv of Me(3)SiF. The derivatives 11b-14b with a 2,2,6,6-tetramethylpiperidinio substituent instead of the dimethylammonio group were prepared analogously, starting from F(3)MeSiCH(2)NR(2)H (NR(2)H = 2,2,6,6-tetramethylpiperidinio). Single-crystal X-ray diffraction studies showed that the Si-coordination polyhedra of 11a.1.5CH(3)CN, 12a-14a, and 11b-14b are distorted trigonal bipyramids, the axial positions being occupied by the fluorine atom and one of the two oxygen atoms (12a/12b, carboxylate oxygen atom; 13a/13b, carbon-linked oxygen atom). These results are in agreement with the NMR data ((1)H, (13)C, (19)F, (29)Si) obtained for these compounds in solution. The chiral (C(1) symmetry) zwitterions 11a-14a and 11b-14b exist as pairs of (A)- and (C)-enantiomers in solution. VT (1)H NMR studies with 11b-14b in CH(3)CN in the temperature range 25-85 degrees C gave no indications for an enantiomerization process [(A)/(C)-enantiomerization] at the silicon atom. 相似文献
Oligonucleotides can be covalently linked to peptides composed of any sequence of amino acids by solid phase fragment condensation. The peptides incorporated into the conjugates include nuclear localizing signals (NLS), nuclear export signals (NES), membrane fusion domain of some viral proteins and some designed peptides with amphipathic character. Evaluation of biological properties of DNA-peptide conjugates indicated that (a) the conjugates could bind to target RNA and dsDNA with increased affinity, (b) the conjugates were more resistant to cellular nuclease degradation, (c) the conjugate-RNA hybrids could activate RNase H as effectively as native oligonucleotides, (d) the conjugates with fusion peptides showed largely enhanced cellular uptake, (e) the conjugates with NLS could be predominantly delivered into the cell nucleus, (f) the conjugates with NES could be localized in the cytoplasm. As a result, antisense oligonucleotides conjugated with NLS could inhibit human telomerase in human leukemia cells much more strongly than phosphorothioate oligonucleotides. 相似文献
N‐t‐Butylacetamidines 1 on heating with methyl vinyl ketone, acrolein or crotonaldehyde gave the 2,3‐dihydropyridine derivatives 4,5 or 6 via N‐alkylation of the acetamidines 1 . Reaction of amidines 1 with phenyl 1‐propenyl ketone, benzalacetone or chalcone gave 3,4‐dihydropyridine derivatives 8, 9 or 10 . These were obtained by C‐alkylation, achieved by Michael addition of the acetamidines 1 as their N,C‐tautomers ene‐1,1‐diamines 1 ′ to α,β‐unsaturated carbonyl compounds, and subsequent cyclodehydration of adducts. Reaction of 1 with ethyl 3‐benzoylacrylate gave 3,4‐dihydropyrrol‐2‐one derivatives 13 . 相似文献
This study reports a facile and practical means to non‐invasively deliver biologically active ingredients through the skin using polymer‐based nanocarriers. For this, polymer nanocapsules were fabricated with different surface charges as well as glass transition temperatures and we observed their ability to deliver the encapsulated active ingredient, coenzyme Q10, through the skin layer. Direct imaging of a probe molecule, Nile Red, and a matrix polymer labeled with fluorescence moiety, Lucifer Yellow, allowed us to demonstrate that the probe molecule readily permeates into the deep skin, while the matrix polymer stays in the stratum corneum layer due to electrostatic interactions. Quantitative characterization of the penetrating amount of coenzyme Q10 using the Frantz cell method proved that, to achieve improved delivery efficiency, the nanocapsule should have a low glass transition temperature as well as positive surface charges.
New diverse N‐aryl‐N‐[1‐furyl(thienyl)but‐3‐enyl]amines (homoallylamines) or 2‐(N‐arylmethylamino)‐2‐furyl(thienyl)acetonitriles (α‐aminonitriles) were easily prepared in good to excellent yields by an indium‐mediated Barbier‐type reaction between N‐hetarylaldimines and allyl bromide in MeOH or a direct three component reaction between anilines, hetaryl aldehydes and trimethylsilyl cyanide in the presence of a catalytic amount of molecular iodine at room temperature, respectively. The entire set of amines was characterized by IR, 1H and 13C NMR spectroscopy. 相似文献
Two series of indomethacin conjugates with D-glucosamine were prepared with the objectives of reducing ulcerogenic potency, increasing the bioavailability of indomethacin and exerting the coordinative effects on osteoarthritis. The structures of the conjugates were identified by ^1H NMR and ^13C NMR. The ester conjugates inhibited edema as potent as indomethacin. 相似文献
Highly monodisperse crosslinked core‐shell polymer microspheres could be prepared easily by introducing special crosslinking reagents into the segregated core in block copolymer assembly films. The crosslinked core was stabilized sterically by highly branched shell chains in solution. These microspheres moved like pseudo‐latex. The microspheres formed a lattice with a body‐centered cubic (BCC) structure near the overlap threshold (C*). This structure changed to a face‐centered cubic (FCC) lattice in the bulk region of the films. Photofunctionalized core‐shell microspheres were prepared by introducing dithiocarbamate (DC) groups into shell parts by means of polymer reactions, where DC groups could be propagated using vinyl monomers such as methyl methacrylate (MMA) with living radical mechanism. Polymeric superstructure (three microphase‐separated structure) films were constructed by graft copolymerization of MMA initiated with photofunctionalized microspheres such as macroinitiators under UV irradiation, exhibiting self‐coloring due to Bragg diffraction. These materials can be used for the construction of optical devices such as for the fabrication of light modulators.
Photograph of a solution of the microsphere in MMA. 相似文献
Chemistry of Natural Compounds - A novel series of diosgenin-triazole conjugates (10a–d, 11a–c, 12a–c, 13a–c) was designed and synthesized as antifungal agents by using a... 相似文献