Search results for "Cyst"

Poly(S-ethylsulfonyl-l-homocysteine): An α-Helical Polypeptide for Chemoselective Disulfide Formation

2018

Homocysteine and cysteine are the only natural occurring amino acids that are capable of disulfide bond formations in peptides and proteins. The chemoselective formation of asymmetric disulfide bonds, however, is chemically challenging and requires an activating group combining stability against hard nucleophiles, e.g., amines, with reactivity toward thiols and soft nucleophiles. In light of these considerations, we introduced the S-alkylsulfonyl cysteines in our previous work. Here, we present the synthesis and ring-opening polymerization of S-ethylsulfonyl-l-homocysteine N-carboxyanhydrides. We demonstrate that the polymerization leads to narrowly distributed polypeptides (Đ = 1.1–1.3) wi…

Poly(S-ethylsulfonyl-l-cysteines) for Chemoselective Disulfide Formation

2016

The amino acid cysteine possesses a unique role in nature due to its ability to reversibly cross-link proteins. To transfer this feature to polypeptides and control the process of disulfide formation, a protective group needs to provide stability against amines during synthesis, combined with chemoselective reactivity toward thiols. A protective group providing these unique balance of stability and reactivity toward different nucleophiles is the S-alkylsulfonyl group. In this work we report the polymerization of S-ethylsulfonyl-l-cysteine N-carboxyanhydride and kinetic evaluations with respect to temperature (−10, 0, and +10 °C) and monomer concentration. The polymerization degree of poly(S…

2020

The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT…

Identification, Characterization and Synthesis of Natural Parasitic Cysteine Protease Inhibitors – More Potent Falcitidin Analogs

2021

ABSTRACTProtease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was the first member of a new class of inhibitors of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum. Using a metabolomics dataset of 25 Chitinophaga strains for molecular networking enabled identification of over 30 natural analogs of falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, and C-terminal functionalization; therefore, they were grouped into the four falcitidin peptide families A-D. The isolation, characterization and absolute st…

Selenoproteins, cholesterol-lowering drugs, and the consequences: revisiting of the mevalonate pathway.

2004

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and peroxisome proliferator-activated receptor alpha activators (fibrates) are the backbone of pharmacologic hypercholesterolemia and dyslipidemia treatment. Many of their clinical effects, however, are still enigmatic. This article describes how a side road of the mevalonate pathway, characterized in recent years, can rationalize a major fraction of these unexplained observations. This side road is the enzymatic isopentenylation of selenocysteine-tRNA([Ser]Sec) (Sec-tRNA), the singular tRNA to decode the unusual amino acid selenocysteine. The functionally indispensable isopentenylation of Sec-tRNA requires a unique interm…

Identification of the membrane penetrating domain of Vibrio cholerae cytolysin as a β-barrel structure

2005

Summary Vibrio cholerae cytolysin (VCC) is an oligomerizing pore-forming toxin that is related to cytolysins of many other Gram-negative organisms. VCC contains six cysteine residues, of which two were found to be present in free sulphydryl form. The positions of two intramolecular disulphide bonds were mapped, and one was shown to be essential for correct folding of protoxin. Mutations were created in which the two free cysteines were deleted, so that single cysteine substitution mutants could be generated for site-specific labelling. Employment of polarity-sensitive fluorophores identified amino acid side-chains that formed part of the pore-forming domain of VCC. The sequence commenced at…

Foetidissimosides C–F, Novel Glycosides from the Roots ofCucurbita foetidissima

2004

Two novel echinocystic acid (=(3β,16α)-3,16-dihydroxyolean-12-en-28-oic acid) glycosides, foetidissimosides C (1), and D (2), along with new cucurbitane glycosides, i.e., foetidissimosides E/F (3/4) as an 1 : 1 mixture of the (24R)/(24S) epimers, were obtained from the roots of Cucurbita foetidissima. Their structures were elucidated by means of a combination of homo- and heteronuclear 2D-NMR techniques (COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC), and by FAB-MS. The new compounds were characterized as (3β,16α)-28-{[O-β-D-glucopyranosyl-(13)-O-β-D-xylopyranosyl-(14)-O-6-deoxy-α-L-mannopyranosyl-(12)-α-L-arabinopyranosyl]oxy}-16-hydroxy-28-oxoolean -12-en-3-yl β-D-glucopyranosiduronic acid (1…

Foetidissimosides C—F, Novel Glycosides from the Roots of Cucurbita foetidissima.

2004

Two novel echinocystic acid (=(3β,16α)-3,16-dihydroxyolean-12-en-28-oic acid) glycosides, foetidissimosides C (1), and D (2), along with new cucurbitane glycosides, i.e., foetidissimosides E/F (3/4) as an 1 : 1 mixture of the (24R)/(24S) epimers, were obtained from the roots of Cucurbita foetidissima. Their structures were elucidated by means of a combination of homo- and heteronuclear 2D-NMR techniques (COSY, TOCSY, NOESY, ROESY, HSQC, and HMBC), and by FAB-MS. The new compounds were characterized as (3β,16α)-28-{[O-β-D-glucopyranosyl-(13)-O-β-D-xylopyranosyl-(14)-O-6-deoxy-α-L-mannopyranosyl-(12)-α-L-arabinopyranosyl]oxy}-16-hydroxy-28-oxoolean -12-en-3-yl β-D-glucopyranosiduronic acid (1…

Insect Immunity

2001

Two novel antimicrobial peptides, which we propose to name termicin and spinigerin, have been isolated from the fungus-growing termite Pseudacanthotermes spiniger (heterometabole insect, Isoptera). Termicin is a 36-amino acid residue antifungal peptide, with six cysteines arranged in a disulfide array similar to that of insect defensins. In contrast to most insect defensins, termicin is C-terminally amidated. Spinigerin consists of 25 amino acids and is devoid of cysteines. It is active against bacteria and fungi. Termicin and spinigerin show no obvious sequence similarities with other peptides. Termicin is constitutively present in hemocyte granules and in salivary glands. The presence of …

Water residence time and the dynamics of toxic cyanobacteria

2012

SUMMARY 1. Climate change affects aquatic ecosystems differently depending on local conditions. In the Mediterranean region, predicted drier seasons could especially affect lake water residence time and in consequence cyanobacteria and cyanotoxin dynamics. 2. We carried out a 3-year study of a shallow, Mediterranean lake (Lake Albufera, Spain), to study the effects of water residence time and other drivers on the dynamics of harmful cyanobacteria and microcystin concentrations (MCYST). 3. Longer water residence time in dry years and dry seasons increased total cyanobacteria biomass, Microcystis aeruginosa populations and MCYST concentrations in the lake water and seston. Droughts increased …