Abstract We describe the synthesis of a trifunctional scaffold constructed from planar core trimesic acid derivatized with three propargylamine moieties. The was attached to solid‐phase resin through carboxylic group fluorinated alkyl spacer arm. orthogonal protection two alkyne groups triethylsilyl and triisopropylsilyl moieties enabled modular efficient derivatization different azides by using on amphiphilic ChemMatrix resin. showed that fluorine label can be used quantify content...

Engineering, procurement and construction (EPC) contracts are on the way to become most usual form of contracting applied by private sector undertake works large scale infrastructure projects. In every project, it is necessary have good contract management in place; otherwise can negative consequences for all parties involved – client, contractor, lenders, government, etc. If not implemented controlled properly, may a impact project as whole. Such failures include delayed schedule, cost...

We designed a combinatorial library of trifunctional scaffold-derived compounds, which were derivatized with 30 different in-house-made azides. The compounds proposed to mimic insulin receptor (IR)-binding epitopes in the molecule and bind activate this receptor. This work has enabled us test our synthetic biological methodology prove its robustness reliability for solid-phase synthesis testing libraries compounds. Our effort resulted discovery two able weakly induce autophosphorylation IR...

Human insulin-like growth factor 1 (IGF-1) is a 70 amino acid protein hormone, with key impact on growth, development, and lifespan. The physiological clinical importance of IGF-1 prompted challenging chemical biological trials toward the development its analogs as molecular tools for receptor (IGF1-R) studies new therapeutics. Here, we report method total synthesis analogs, which entails solid-phase two precursor chains that followed by CuI-catalyzed azide-alkyne cycloaddition ligation...

The rise of CuI‐catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives amino acid as precursors the synthesis clicked peptides. However, use acids in peptide is complicated by their high cost. For this reason, we investigated possibility in‐house preparation a set five Fmoc acids: β ‐azido l ‐alanine d ‐alanine, γ ‐homoalanine, δ ‐ornithine ω ‐lysine. We several reaction pathways described literature, suggested improvements proposed alternative routes...

Abstract In the enantiomeric separation of highly polar compounds, a traditionally challenging task for high‐performance liquid chromatography, ion‐exchange chiral stationary phases have found main field application. this contribution, we present series novel anion‐exchange‐type enantiomer protected amino phosphonates and N‐protected acids. Two prepared selectors possessed double triple bond within single molecule. Thus, they were immobilized onto silica support employing either thiol‐ene...

We present a trifunctional scaffold designed for the solid-phase synthesis of trimodal compounds. This holds two alkyne arms in free and TIPS-protected form consecutive CuAAC (copper(I)-catalyzed azide–alkyne cycloaddition), one Fmoc-protected hydrazide arm reaction with aldehydes, carboxylic acid CF2 groups attachment to resin 19F-NMR quantification. was attached derivatized model azides aliphatic, electron-rich or electron-poor aromatic aldehydes. identified several limitations caused by...

Three potential reactivators of nerve agents-inhibited acetylcholinesterase: 2-[(hydroxyimino)phenylmethyl]-1-methylpyridinium iodide 3a, 2-[(hydroxyimino)pyridin-2-ylmethyl]-1-methylpyridinium 3b and 2-[(1-hydroxyimino) ethyl]-1-methylpyridinium 3c were synthesized. Their reactivation potency was examined using a standard in vitro test. A rat brain homogenate used as the source acetylcholinesterase. compared with currently acetylcholinesterase reactivator - 2-PAM (pralidoxime) 4. All tested...

Reactivators of acetylcholinesterase (AChE; EC 3.1.1.7) are able to treat intoxication by organophosphorus compounds, especially with pesticides or nerve agents. Owing the fact that there exists no universal "broad-spectrum" reactivator organophosphates-inhibited AChE, many laboratories have synthesized new AChE reactivators. Here, we five and three previously known quaternary monopyridinium oximes as potential reactivators inhibited Potencies cleave p-nitrophenyl acetate (PNPA), which is...

Class of monoquaternary pyridinium oximes was in vitro tested as potential reactivators acetylcholinesterase (AChE; EC 3.1.1.7) inhibited by nerve agent sarin. Human brain homogenate used an appropriate source cholinesterases. Reactivation potency novel compared with currently available reactivators—pralidoxime, obidoxime, and HI-6. According to the obtained results, only five were able satisfactorily renew cholinesterase (pralidoxime, HI-6, 4-PAM, K119). Unfortunately, none surpassed...

Ten meta - and para -substituted benzoic acids with substituents N + (CH 3 ) , CH 2 Py SO PO(OCH were synthesized. Dissociation constants of these determined in five solvents (water, ethanol, methanol, -dimethylformamide, dimethyl sulfoxide) at 25 °C. acid derivatives other H, NHCOCH OCH F, Cl, Br, I, COCH CN, NO taken from the literature (calibration set). Substituent σ m p I R i for calculated by nonlinear PLS (partial least-square method latent variables) calibration three correlation...

Aromatic oximes are reduced in aqueous solution a four-electron process. The reducible species the pH range 5−8 is diprotonated form of oxime. This generated course electrolysis vicinity electrode surface from adsorbed neutral reduction initiated by cleavage N−O bond. diprotonation facilitates process preformation OH2+ as good leaving group and positive charge on azomethine nitrogen. Diprotonation has been proven based shapes i = f(pH) plots, observed shifts half-wave potentials with...

Ligands containing bulky aliphatic P1 residues exhibit a high affinity towards cytosolic leucine aminopeptidase, bizinc protease of biomedical significance. According to this specificity, series phosphonic and phosphinic compounds have been put forward as novel putative inhibitors the enzyme. These were derivatives methionine norleucine both single amino acids dipeptides. The designed synthesised tested peptidase isolated from porcine kidneys using an improved separation procedure affording...

Multi‐orthogonal scaffolds can be useful for the attachment of several different compounds to same central skeleton. Such find applications in development protein mimics because their potential mimic distant epitopes structure. Three new tri‐orthogonal variants a previously reported scaffold have been developed that are suitable solid‐phase synthesis three peptides on Different chemical moieties were combined phased amino acids scaffolds: Fmoc‐ or Alloc‐protected amine, free TIPS‐protected...

Insulin and insulin-like growth factor 1 (IGF-1) are closely related hormones involved in the regulation of metabolism growth. They elicit their functions through activation tyrosine kinase-type receptors: insulin receptors (IR-A IR-B) IGF-1 receptor (IGF-1R). Despite similarity primary three-dimensional structures, bind noncognate with substantially reduced affinity. We prepared [d-HisB24, GlyB31, TyrB32]-insulin, which binds all three high affinity (251 or 338% binding to IR-A respectively...

Insulin is a lifesaver for millions of diabetic patients. There need new insulin analogues with more physiological profiles and that will be thermally stable than human insulin. Here, we describe the chemical engineering 48 were designed to have changed binding specificities toward isoforms A B receptor (IR-A IR-B). We systematically modified at C-terminus B-chain, N-terminus A-chain, A14 A18 positions. discovered an analogue has Cα-carboxyamidated Glu B31 Ala B29 3-fold-enhanced specificity...