67 research outputs found
Solid phase synthesis of functionalised SAM-forming alkanethiol-oligoethyleneglycols
We present an efficient solid phase synthesis methodology that provides easy access to a range of functionalised long-chain alkanethiol-oligoethyleneglycols that form well-defined self-assembled monolayers on gold and are compatible with pre- or post-assembly conjugation of (bio)molecules. We demonstrate the versatility of our synthetic route by synthesising LCAT-OEGs with a range of functional moieties, including peptides, electro-active redox groups, chemical handles for post-assembly conjugation of (bio)molecules, and demonstrate the application of our LCAT-OEG monolayers in immunosensing, where they show good biocompatibility with minimal biofouling
Uridine-derived ribose fuels glucose-restricted pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox balance, survival and proliferation in glucose-restricted PDA cells. In PDA, UPP1 is regulated by KRAS-MAPK signalling and is augmented by nutrient restriction. Consistently, tumours expressed high UPP1 compared with non-tumoural tissues, and UPP1 expression correlated with poor survival in cohorts of patients with PDA. Uridine is available in the tumour microenvironment, and we demonstrated that uridine-derived ribose is actively catabolized in tumours. Finally, UPP1 deletion restricted the ability of PDA cells to use uridine and blunted tumour growth in immunocompetent mouse models. Our data identify uridine utilization as an important compensatory metabolic process in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy
Review of the Palaearctic species of Ismaridae Thomson, 1858 (Hymenoptera: Diaprioidea)
This is an open access article, available to all readers online, published under a Creative Commons BY-NC-ND license: https://creativecommons.org/licenses/by-nc-nd/3.0/. The attached file is the published version of the article
Synthesis of a photo-caged aminooxy alkane thiol
A photo-caged aminooxy alkane thiol synthesized in 7 steps and 15% overall yield was used to form a self-assembled monolayer (SAM). Photo-deprotection on the surface was confirmed by FT-IR spectroscopy and contact angle goniometry. Conjugation of a small molecule ketone, ethyl levulinate, further confirmed the presence of aminooxy groups on the surface
Aminooxy End-Functionalized Polymers Synthesized by ATRP for Chemoselective Conjugation to Proteins
Site-specific protein immobilization through N-terminal oxime linkages
Immobilizing proteins in specific orientations is important for diagnostic protein arrays, biomaterials, and other applications where retention of bioactivity is essential. We report an approach for protein micropatterning that exploits a chemoselective reaction to conjugate proteins at the N-terminus to polymer films. A copolymer from 2-hydroxyethyl methacrylate and a Boc-protected aminooxy tetra(ethylene glycol) methacrylate was synthesized by radical polymerization. Boc groups were locally deprotected using photoacid generator-based photolithography. Micropatterns were verified by fluorescence microscopy utilizing green fluorescent aldehyde microspheres. Streptavidin that was subjected to a transamination reaction to install an -ketoamide group at the N-terminus was conjugated to the patterns by oxime bond formation. Since the majority of proteins may be modified to contain a reactive carbonyl group, this methodology should be applicable to pattern a wide variety of proteins specifically through the N-terminus
Thermoreversibly crosslinked poly(ε-caprolactone) as recyclable shape-memory polymer network
A new concept to build shape memory polymers (SMP) combining outstanding fixity and recovery ratios (both above 99% after only one training cycle) typical of chemically crosslinked SMPs with reprocessability restricted to physically crosslinked SMPs is demonstrated by covalently bonding, through thermoreversible Diels–Alder (DA) adducts, star-shaped poly(epsilon-caprolactones) (PCL) end-functionalized by furan and maleimide moieties. A PCL network is easily prepared by melt-blending complementary end-functional star polymers in retro DA regime, then by curing at lower temperature to favour the DA cycloaddition. Such covalent network can be reprocessed when heated again at the retro DA temperature. The resulting SMP shows still excellent shape memory properties attesting for its good recyclability
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