Well-defined protein-polymer conjugates—synthesis and potential applications

During the last decades, numerous studies have focused on combining the unique catalytic/functional properties and structural characteristics of proteins and enzymes with those of synthetic molecules and macromolecules. The aim of such multidisciplinary studies is to improve the properties of the natural component, combine them with those of the synthetic, and create novel biomaterials in the nanometer scale. The specific coupling of polymers onto the protein structures has proved to be one of the most straightforward and applicable approaches in that sense. In this article, we focus on the synthetic pathways that have or can be utilized to specifically couple proteins to polymers. The different categories of well-defined protein-polymer conjugates and the effect of the polymer on the protein function are discussed. Studies have shown that the specific conjugation of a synthetic polymer to a protein conveys its physico-chemical properties and, therefore, modifies the biodistribution and solubility of the protein, making it in certain cases soluble and active in organic solvents. An overview of the applications derived from such bioconjugates in the pharmaceutical industry, biocatalysis, and supramolecular nanobiotechnology is presented at the final part of the articl

Biofunctionality with a twist: the importance of molecular organisation, handedness and configuration in synthetic biomaterial design

The building blocks of life – nucleotides, amino acids and saccharides – give rise to a large variety of components and make up the hierarchical structures found in Nature. Driven by chirality and non-covalent interactions, helical and highly organised structures are formed and the way in which they fold correlates with specific recognition and hence function. A great amount of effort is being put into mimicking these highly specialised biosystems as biomaterials for biomedical applications, ranging from drug discovery to regenerative medicine. However, as well as lacking the complexity found in Nature, their bio-activity is sometimes low and hierarchical ordering is missing or underdeveloped. Moreover, small differences in folding in natural biomolecules (e.g., caused by mutations) can have a catastrophic effect on the function they perform. In order to develop biomaterials that are more efficient in interacting with biomolecules, such as proteins, DNA and cells, we speculate that incorporating order and handedness into biomaterial design is necessary. In this review, we first focus on order and handedness found in Nature in peptides, nucleotides and saccharides, followed by selected examples of synthetic biomimetic systems based on these components that aim to capture some aspects of these ordered features. Computational simulations are very helpful in predicting atomic orientation and molecular organisation, and can provide invaluable information on how to further improve on biomaterial designs. In the last part of the review, a critical perspective is provided along with considerations that can be implemented in next-generation biomaterial designs

A Peptide Amphiphile Organogelator of Polar Organic Solvents

A peptide amphiphile is reported, that gelates a range of polar organic solvents including acetonitrile/water, N,N-dimethylformamide and acetone, in a process dictated by β-sheet interactions and facilitated by the presence of an alkyl chain. Similarities with previously reported peptide amphiphile hydrogelators indicate analogous underlying mechanisms of gelation and structure-property relationships, suggesting that peptide amphiphile organogel design may be predictably based on hydrogel precedents

A Liposome-Micelle-Hybrid (LMH) Oral Delivery System for Poorly Water-Soluble Drugs: Enhancing Solubilisation and Intestinal Transport

A novel liposome-micelle-hybrid (LMH) carrier system was developed as a superior oral drug delivery platform compared to conventional liposome or micelle formulations. The optimal LMH system was engineered by encapsulating TPGS micelles in the aqueous core of liposomes and its efficacy for oral delivery was demonstrated using lovastatin (LOV) as a model poorly soluble drug with P-gp (permeability glycoprotein) limited intestinal absorption. LOV-LMH was characterised as unilamellar, spherical vesicles encapsulating micellar structures within the interior aqueous core and showing an average diameter below 200 nm. LMH demonstrated enhanced drug loading, water apparent solubility and extended/controlled release of LOV compared to conventional liposomes and micelles. LMH exhibited enhanced LOV absorption and transportation in a Caco-2 cell monolayer model of the intestine by inhibiting the P-gp transporter system compared to free LOV. The LMH system is a promising novel oral delivery approach for enhancing bioavailability of poorly water-soluble drugs, especially those presenting P-gp effluxes limited absorption

Enhanced mechanical and thermal strength in mixed enantiomers based supramolecular gel

Mixing supramolecular gels based on enantiomers leads to re-arrangement of gel fibers at the molecular level, which results in more favorable packing and tuneable properties. Bis(urea) compounds tagged with a phenylalanine methyl ester in racemic and enantiopure forms were syn-thesized. Both enantiopure and racemate compounds formed gels in a wide range of solvents and the racemate (1-rac) formed a stronger gel network compared to the enantiomers. The gel (1R+1S) obtained by mixing equimolar amount of enantiomers (1R and 1S) showed enhanced mechanical and thermal stability compared to enantiomers and racemate gels. The preservation of chirality in these compounds was analyzed by circular dichroism and optical rotation measurements. Analysis of the SEM and AFM images revealed that the network in the mixed gel is a combination of enantiomers and racemate fibers, which was further supported by solid state NMR. The analysis of the packing in xerogels by solid state NMR spectra and the existence of twisted-tape morphology in SEM and AFM images confirmed the presence of both self-sorted and co-assembled fibers in mixed gel. The enhanced thermal and mechanical strength may be attributed to the enhanced intermolecular forces between the racemate and enantiomer and the combination of both self-sorted and co-assembled enantiomers in the mixed gel.We thank University of Iceland Research Fund for financial support. D.G. thanks University of Iceland for the Doctoral Research grant and Z.K. thanks University of Ljubljana for the Erasmus exchange program. We thankfully acknowledge Dr. A. Rawal, The Mark Wainwright Analytical Centre, UNSW for solid state NMR studies and Dr. Sigrídur Jónsdóttir, University of Iceland for solution NMR and Mass spectroscopy. P.T. thanks the Australian Research Council for an ARC Centre of Excellence grant (CE140100036) and A.D.M. thanks the National Health and Medical Research Council for a Dementia Development Research Fellowship (APP1106751). L.F. and A.V. thank the FCT (UID/BIO/04469/2013), COMPETE 2020 (POCI-01-0145-FEDER-006684), and Norte2020 Programa Operacional Regional do Norte (BioTecNorte operation, NORTE-01-0145-FEDER-000004) for rheological studies. The rheological study was supported by a STSM Grant from COST Action CM1402 Crystallize.info:eu-repo/semantics/publishedVersio

Dynamics of Sticky Information and Sticky Price Models in a New Keynesian DSGE Framework

Recent literature on monetary policy analysis extensively uses the sticky price model of price adjustment in a New Keynesian Macroeconomic framework. This price setting model, however, has been criticized for producing implausible results regarding inflation and output dynamics. This paper examines and compares dynamic responses of the sticky price and sticky information models to a cost-push shock in a New Keynesian DSGE framework. It finds that the sticky information model produces more reasonable dynamics through lagged, gradual and hump-shaped responses to a shock as observed in data. However, these responses depend on the persistence of the shock

A diverse view of science to catalyse change

Valuing diversity leads to scientific excellence, the progress of science and, most importantly, it is simply the right thing to do. We must value diversity not only in words, but also in actions

A diverse view of science to catalyse change:Valuing diversity leads to scientific excellence, the progress of science and, most importantly, it is simply the right thing to do. we must value diversity not only in words, but also in actions

No abstract available.publishe

Polymersomes as protocellular constructs

\u3cp\u3eDespite the rapidly growing amount of knowledge on the structure and function of cells, they remain a distant bottom-up synthetic target due to their overwhelming complexity. A path to this goal is the development of protocellular systems that approximate one or more aspects of a natural cell. Polymer vesicles, or polymersomes, are an attractive scaffold for protocellular constructs, due to our ability to engineer the polymer membrane and generate a wide range of properties. This article summarizes the current state of polymersome science with respect to the properties and functions that lend these polymer-based systems to applications in synthetic cell research.\u3c/p\u3

Synthesis of protein bioconjugates via cysteine-maleimide chemistry

\u3cp\u3eThe chemical linking or bioconjugation of proteins to fluorescent dyes, drugs, polymers and other proteins has a broad range of applications, such as the development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent microscopy and systems chemistry. For many of these applications, specificity of the bioconjugation method used is of prime concern. The Michael addition of maleimides with cysteine(s) on the target proteins is highly selective and proceeds rapidly under mild conditions, making it one of the most popular methods for protein bioconjugation. We demonstrate here the modification of the only surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II) bisterpyridine maleimide. The protein bioconjugation is verified by gel electrophoresis and purified by aqueous-based fast protein liquid chromatography in 27% yield of isolated protein material. Structural characterization with MALDI-TOF MS and UV-Vis is then used to verify that the bioconjugation is successful. The protocol shown here is easily applicable to other cysteine - maleimide coupling of proteins to other proteins, dyes, drugs or polymers.\u3c/p\u3