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Maryam Oroujeni Sara S. Rinne Anzhelika Vorobyeva Annika Loftenius Joachim Feldwisch Per Jonasson Vladimir Chernov Anna Orlova Fredrik Y. Frejd Vladimir Tolmachev 《International journal of molecular sciences》2021,22(5)
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies. 相似文献
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Nicki Frederiksen Assoc. Prof. Paul R. Hansen Dr. Dorota Zabicka Magdalena Tomczak Malgorzata Urbas Dr. Ilona Domraceva Prof. Fredrik Björkling Assoc. Prof. Henrik Franzyk 《ChemMedChem》2020,15(24):2544-2561
The influence of hydrophobicity on antibacterial activity versus the effect on the viability of mammalian cells for peptide/peptoid hybrids was examined for oligomers based on the cationic Lys-like peptoid residue combined with each of 28 hydrophobic amino acids in an alternating sequence. Their relative hydrophobicity was correlated to activity against both Gram-negative and Gram-positive species, human red blood cells, and HepG2 cells. This identified hydrophobic side chains that confer potent antibacterial activity (e. g., MICs of 2–8 μg/mL against E. coli) and low toxicity toward mammalian cells (<10 % hemolysis at 400 μg/mL and IC50>800 μg/mL for HepG2 viability). Most peptidomimetics retained activity against drug-resistant strains. These findings corroborate the hypothesis that for related peptidomimetics two hydrophobicity thresholds may be identified: i) it should exceed a certain level in order to confer antibacterial activity, and ii) there is an upper limit, beyond which cell selectivity is lost. It is envisioned that once identified for a given subclass of peptide-like antibacterials such thresholds can guide further optimisation. 相似文献
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Poly(lactic acid) (PLA)/kraft pulp fiber (30 wt%) composites were prepared with and without a coupling agent (epoxidized linseed oil, ELO, 1.5 wt%) by injection molding. The non-annealed composite samples, along with lean PLA, were exposed to two hydro-thermal conditions: cyclic 50% RH/90% RH at 23 and 50°C, both up to 42 days. The aging effects were observed by size exclusion chromatography, differential scanning calorimetry, dynamic and tensile mechanical analysis, and fracture surface imaging. ELO temporarily accelerated the material's internal transition from viscous to an increasingly elastic response during the aging at 50°C. ELO also slowed down the tensile strength reduction of the composites at 50°C. These observations were explained with the hydrophobic ELO molecules' coupling and plasticizing effects at fiber/matrix interfaces. No effects were observed at 23°C. 相似文献
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Effects of breed and age at slaughter on degradation of muscle lipids during processing of dry‐cured hams 下载免费PDF全文
Linda Storrustløkken Hanne Marie Devle Lars Erik Gangsei Carl Fredrik Naess‐Andresen Bjørg Egelandsdal Ole Alvseike Dag Ekeberg 《International Journal of Food Science & Technology》2015,50(8):1933-1943
Hams from Landrace, Duroc and Hampshire pigs slaughtered at ages 6, 7.5 and 9 months were processed to generate Norwegian Parma‐style hams. Lipid contents and the compositions of fatty acid classes (ΣSFA, ΣMUFA, ΣPUFA) within neutral lipids, phospholipids and free fatty acids were determined. Small differences in lipid degradation and composition of the classes were revealed. However, significant sensory differences related to lipids were observed. Breed was more important than age. Dry‐cured Hampshire hams gave a more intense mature odour that may be associated with higher overall lipid degradation. Unexpectedly, these hams also demonstrated high juiciness and tenderness, which could be related to the melting characteristics of the fat. Dry‐cured Duroc hams showed a higher susceptibility towards rancidity, presumably associated with preferential oxidation of n‐6 fatty acids relative to C18:1 n‐9. Dry‐cured Landrace hams showed the lowest juiciness and tenderness, likely due to their lower fat content (marbling). 相似文献
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Dragos Horvath Michael Lisurek Bernd Rupp Ronald Kühne Edgar Specker Jens von Kries Didier Rognan C. David Andersson Fredrik Almqvist Mikael Elofsson Per‐Anders Enqvist Anna‐Lena Gustavsson Nikita Remez Jordi Mestres Gilles Marcou Alexander Varnek Marcel Hibert Jordi Quintana Ronald Frank 《ChemMedChem》2014,9(10):2309-2326
This work describes a collaborative effort to define and apply a protocol for the rational selection of a general‐purpose screening library, to be used by the screening platforms affiliated with the EU‐OPENSCREEN initiative. It is designed as a standard source of compounds for primary screening against novel biological targets, at the request of research partners. Given the general nature of the potential applications of this compound collection, the focus of the selection strategy lies on ensuring chemical stability, absence of reactive compounds, screening‐compliant physicochemical properties, loose compliance to drug‐likeness criteria (as drug design is a major, but not exclusive application), and maximal diversity/coverage of chemical space, aimed at providing hits for a wide spectrum of drugable targets. Finally, practical availability/cost issues cannot be avoided. The main goal of this publication is to inform potential future users of this library about its conception, sources, and characteristics. The outline of the selection procedure, notably of the filtering rules designed by a large committee of European medicinal chemists and chemoinformaticians, may be of general methodological interest for the screening/medicinal chemistry community. The selection task of 200K molecules out of a pre‐filtered set of 1.4M candidates was shared by five independent European research groups, each picking a subset of 40K compounds according to their own in‐house methodology and expertise. An in‐depth analysis of chemical space coverage of the library serves not only to characterize the collection, but also to compare the various chemoinformatics‐driven selection procedures of maximal diversity sets. Compound selections contributed by various participating groups were mapped onto general‐purpose self‐organizing maps (SOMs) built on the basis of marketed drugs and bioactive reference molecules. In this way, the occupancy of chemical space by the EU‐OPENSCREEN library could be directly compared with distributions of known bioactives of various classes. This mapping highlights the relevance of the selection and shows how the consensus reached by merging the five different 40K selections contributes to achieve this relevance. The approach also allows one to readily identify subsets of target‐ or target‐class‐oriented compounds from the EU‐OPENSCREEN library to suit the needs of the diverse range of potential users. The final EU‐OPENSCREEN library, assembled by merging five independent selections of 40K compounds from various expert groups, represents an excellent example of a Europe‐wide collaborative effort toward the common objective of building best‐in‐class European open screening platforms. 相似文献
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Huang Kevin Chitrakar Digesh Rydén Fredrik Chizeck Howard Jay 《Intelligent Service Robotics》2019,12(4):289-301
Intelligent Service Robotics - This work presents a user-study evaluation of various visual and haptic feedback modes on a real telemanipulation platform. Of particular interest is the potential... 相似文献
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