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

Face-selectivity in [4+2]-cycloadditions to novel polycyclic benzoquinones. Remarkable stereodirecting effects of a remote cyclopropane ring and an olefinic bond

π-Face selectivity in Diels-Alder reactions between specially crafted bicyclo[2.2.2]octane-fused benzoquinones, where the dienophilic moiety is imbedded in an isosteric environment, can be modulated by a remote olefinic bond and a cyclopropane ring. Quantum mechanical calculations while reproducing the observed diastereoselectivities at the TS level indicate the involvement of ground state orbital effects

Extended π-conjugated pyrene derivatives: structural, photophysical and electrochemical properties

This article presents a set of extended π-conjugated pyrene derivatives, namely 1,3-di(arylethynyl)-7-tert-butylpyrenes, which were synthesized by a Pd-catalyzed Sonogashira coupling reaction of 1,3-dibromo-7-tert-butylpyrenes with the corresponding arylethynyl group in good yields. Despite the presence of the tert-butyl group located at the 7-position of pyrene, X-ray crystallographic analyses show that the planarity of the Y-shaped molecules still exhibits strong face-to-face π-π stacking in the solid state; all of the compounds exhibit blue or green emission with high quantum yields (QYs) in dichloromethane. DFT calculations and electrochemistry revealed that this category of compound possesses hole-transporting characteristics. In addition, with strong electron-donating (-N(CH₃)₂) or electron-withdrawing (-CHO) groups in 2 d or 2 f, these molecules displayed efficient intramolecular charge-transfer (ICT) emissions with solvatochromic shifts from blue to yellow (green) on increasing the solvent polarity. Furthermore, the compounds 2 d and 2 f possess strong CT characteristics

Simultaneous control of emission localization and two-photon absorption efficiency in dissymmetrical chromophores

C. K's secondary address for this work: CNRS UMR6082 FOTON, INSA de Rennes, 20 avenue des Buttes de Coësmes, CS 70839, 35708 RENNES cedex 7, FranceWe thank E. Leroux for technical assistance in the synthesis, S. Soualmi in electrochemical mesaurements and M. H. V. Werts for help in the TPEF measurements.International audienceThe aim of the present work is to demonstrate that combined spatial tuning of fluorescence and two-photon absorption (TPA) properties of multipolar chromophores can be achieved by introduction of slight electronic chemical dissymmetry. In that perspective, two model series of structurally related chromophores have been designed and investigated. One is based on rod-like quadrupolar chromophores bearing either two identical or different electron-donating (D) end groups and the other on three-branched octupolar chromophores built from a trigonal donating moiety bearing identical or different acceptor (A) peripheral groups. The influence of the electronic dissymmetry is investigated by combined experimental and theoretical studies of the linear and nonlinear optical properties of dissymmetrical chromophores compared to their symmetrical counterparts. In both types of systems (i.e., quadrupoles and octupoles), experiments and theory reveal that excitation is essentially delocalized and that excitation involves synchronized charge redistribution (i.e., concerted intramolecular charge transfer) between the different D and A moieties within the multipolar structure. In contrast, the emission stems only from a particular dipolar subunit bearing the strongest D or A moiety due to fast excitation localization after excitation, prior to emission. Hence, control of emission characteristics (polarization and emission spectrum), can be achieved, in addition to localization, by controlled introduction of electronic dissymmetry (i.e., replacement of one of the D or A end-groups by a slightly stronger D′ or A′ unit). Interestingly, slight dissymmetrical functionalization of both quadrupolar and octupolar compounds does not lead to significant loss in TPA responses and can even be beneficial due to the spectral broadening and peak position tuning that it allows. This study thus reveals an original molecular engineering route allowing TPA enhancement in multipolar structures, due to concerted core-to-periphery or periphery-to-core intramolecular charge redistribution upon excitation, while providing for control of emission localization. Such a route could be extended to more intricate (dendritic) and multipolar (3D) systems

Preparation of silk fibroin–poly(ethylene glycol) conjugate films through click chemistry

Azide silk fibroin (azido SF) and alkyne terminal poly(ethylene glycol) (PEG) 2000 (acetylene-terminal PEG 2000) were synthesized. Azido SF was reacted with acetylene-terminal PEG 2000 to produce films via a copper-mediated 1,3-cycloaddition (‘click’ chemistry) generating a triazole linkage as the networking forming reaction. Through click chemistry, novel silk-based films with various weight ratios were prepared and investigated. Fourier transform infrared, X-ray diffraction and differential scanning calorimetry analyses showed that the ordered association of the PEG molecules is strongly constrained by the presence of the SF molecules and crosslinking and that the presence of acetylene-terminal PEG 2000 in the films induced crystallization to a β-sheet of SF chains.Water content and contact angle measurements indicated that the hydrophilicity of the films increased compared with SF. SF–PEG films exhibited smooth and rough structures, depending on degree of crosslinking and on the weight ratio of SF and PEG, as shown by scanning electron microscopy

Utility of Hemoglobin A1c for Diagnosing Prediabetes and Diabetes in Obese Children and Adolescents

OBJECTIVE-Hemoglobin A(1c) (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking. RESEARCH DESIGN AND METHODS-We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of similar to 2 years in 218 subjects. RESULTS-At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C 6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% Cl 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time. CONCLUSIONS-The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents