Synthesis and purification of peptides

Improved routes to tetrabenzo[a,c,g,i]fluorene derivatives have been developed, allowing the synthesis of Nᵃ-17-tetrabenzo[a,c,g,i]fluorenylmethoxycarbonyl (Tbfmoc) urethane derivatives of alanine, leucine, isoleucine, methionine and valine. The chloroformate and pentafluorophenyl carbonate of 17- tetrabenzo[a,c,g,i]fluorenylmethanol have been prepared and used to introduce the base-labile Tbfmoc group onto the Nᵃ-termini of resin-bound peptides.The high affinity of the Tbfmoc group for porous graphitised carbon (PGC) has been exploited for the purification of a range of synthetic peptides (23-85 residues). A comparison of various basic solvent sytems used to elute the purified peptide from PGC is presented. The hydrophobicity of the Tbfmoc group has been used to simplify the purification of a ubiquitin analogue, UbY59F (76 residues), by the enhanced retention of the Tbfmoc peptide on RP-HPLC.A new synthesis of 2-hydroxydibenzocycloheptadien-5-one has been devised. This compound has been used to develop acid-labile linkers for the synthesis of peptide C-terminal alkyl amides and aza-glycine peptides, compatible with the FmocABu solid phase method. Alternative modes of attachment of the linker to polystyrene resin are compared for the synthesis of bombesin, a peptide amide

What Do You Do Sunday, Mary?

https://digitalcommons.library.umaine.edu/mmb-vp/2649/thumbnail.jp

Mary

https://digitalcommons.library.umaine.edu/mmb-vp/2091/thumbnail.jp

GPR18, GPR55 and GPR119 in GtoPdb v.2023.1

GPR18, GPR55 and GPR119 (provisional nomenclature), although showing little structural similarity to CB1 and CB2 cannabinoid receptors, respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [104]. Although there are multiple reports to indicate that GPR18, GPR55 and GPR119 can be activated in vitro by N-arachidonoylglycine, lysophosphatidylinositol and N-oleoylethanolamide, respectively, there is a lack of evidence for activation by these lipid messengers in vivo. As such, therefore, these receptors retain their orphan status

GPR18, GPR55 and GPR119 (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

GPR18, GPR55 and GPR119 (provisional nomenclature), although showing little structural similarity to CB1 and CB2 cannabinoid receptors, respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [98]. Although there are multiple reports to indicate that GPR18, GPR55 and GPR119 can be activated in vitro by N-arachidonoylglycine, lysophosphatidylinositol and N-oleoylethanolamide, respectively, there is a lack of evidence for activation by these lipid messengers in vivo. As such, therefore, these receptors retain their orphan status

An experimental approach to quantify strain transfer efficiency of fibre bragg grating sensors to host structures

This paper developed a method to evaluate the strain transfer efficiency of fibre Bragg grating sensors to host structures. Various coatings were applied to fibre Bragg grating sensors after being fabricated. They were epoxy, silane agent and polypropylene, representing different surface properties. A neat epoxy resin plate was used as the host in which the coated fibre sensors were embedded in the central layer. The tensile strain output from the FBGs was compared with that obtained from electrical strain gauges which were attached on the surface of the specimen. A calculating method based on the measured strains was developed to quantify the strain transfer function of different surface coatings. The strain transfer coefficient obtained from the proposed method provided a direct indicator to evaluate the strain transfer efficiency of different coatings used on the FBG sensors, under either short or long-term loading. The results demonstrated that the fibre sensor without any coating possessed the best strain transfer, whereas, the worst strain transfer was created by polypropylene coating. Coatings play a most influential role in strain measurements using FBG sensors

A new paradigm evaluating cost per cure of HCV infection in the UK

Background: New interferon (IFN)-free treatments for hepatitis C are more effective, safer but more expensive than current IFN-based therapies. Comparative data of these, versus current first generation protease inhibitors (PI) with regard to costs and treatment outcomes are needed. We investigated the real-world effectiveness, safety and cost per cure of 1st generation PI-based therapies in the UK. Methods: Medical records review of patients within the HCV Research UK database. Patients had received treatment with telaprevir or boceprevir and pegylated interferon and ribavirin (PR). Data on treatment outcome, healthcare utilisation and adverse events (AEs) requiring intervention were collected and analysed overall and by subgroups. Costs of visits, tests, therapies, adverse events and hospitalisations were estimated at the patient level. Total cost per cure was calculated as total median cost divided by SVR rate. Results: 154 patients from 35 centres were analysed. Overall median total cost per cure was £44,852 (subgroup range,: £35,492 to £107,288). Total treatment costs were accounted for by PI: 68.3 %, PR: 26.3 %, AE management: 5.4 %. Overall SVR was 62.3 % (range 25 % to 86.2 %). 36 % of patients experienced treatment-related AEs requiring intervention, 10 % required treatment-related hospitalisation. Conclusions: This is the first UK multicentre study of outcomes and costs of PI-based HCV treatments in clinical practice. There was substantial variation in total cost per cure among patient subgroups and high rates of treatment-related discontinuations, AEs and hospitalisations. Real world safety, effectiveness and total cost per cure for the new IFN free combinations should be compared against this baseline

Tuning Actions and Observables in Lattice QCD

We propose a strategy for conducting lattice QCD simulations at fixed volume but variable quark mass so as to investigate the physical effects of dynamical fermions. We present details of techniques which enable this to be carried out effectively, namely the tuning in bare parameter space and efficient stochastic estimation of the fermion determinant. Preliminary results and tests of the method are presented. We discuss further possible applications of these techniques.Comment: 17 pages, 4 eps figures; affiliation correction in this header + minor post-referee addition