Search results for "Cyst"

Rethinking Cysteine Protective Groups:S-Alkylsulfonyl-l-Cysteines for Chemoselective Disulfide Formation

2016

The ability to reversibly cross-link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S-alkylsulfonyl-l-cysteines and N-carboxy anhydrides (NCA) thereof for peptide synthesis. The S-alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization of the corresponding NCAs yielding well-defined homo- as well as block co-polymers. Yet, thiols react immediately with the S-alkylsulfonyl group forming asymmetric disulfides. Therefore, we introduce the first reactive cysteine derivative for efficient and chemoselective disulfide formation…

2020

Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SNAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly…

Putative identification of an amphipathic alpha-helical sequence in hemolysin of Escherichia coli (HlyA) involved in transmembrane pore formation.

2008

Abstract Escherichia coli hemolysin is a pore-forming protein belonging to the RTX toxin family. Cysteine scanning mutagenesis was performed to characterize the putative pore-forming domain of the molecule. A single cysteine residue was introduced at 48 positions within the sequence spanning residues 170–400 and labeled with the polarity-sensitive dye badan. Spectrofluorimetric analyses indicated that several amino acids in this domain are inserted into the lipid bilayer during pore formation. An amphipathic α-helix spanning residues 272–298 was identified that may line the aqueous pore. The importance of this sequence was highlighted by the introduction of two prolines at positions 284 and…

Mixed micelles composed of Peptides and Gadolinium complexes as tumor-specific contrast agents in MRI: a SANS study

2004

A detailed structural investigation on mixed micelle aggregates as target-specific contrast agents for magnetic resonance imaging technique has been carried out by way of small angle neutron scattering measurements. These mixed micelles are formed by two new amphiphilic molecules formed by a bioactive peptide and a claw moiety. The first molecule, C18H37CONH(AdOO)(x)-G-CCK8 (C18LxCCK8, x = 2, 5), contains an 18-carbon-atom alkylic chain bound to the C-terminal of the cholecystokinin octapeptide amide (CCK 26-33 or CCK8) and is able to bind to the overexpressed CCK receptor of some tumor cells. The second molecule, C(18)H(37)CONHLys(DTPAGlu)CONH25- (C18DTPAGlu) or its gadolinium complex [C(1…

Triplet of cysteines – Coordinational riddle?

2020

Polythiol binding of metal ions plays crucial role in the proper functioning of cysteine-rich proteins that are responsible for metal homeostasis and defending processes against metal toxicity (including heavy metals detoxification). The coordination properties of cysteine residues involved in specific sequencional patterns in proteins (like those present in e.g. metallothioneins) are interesting not only from a chemical point of view but may also lead to a better understanding of the purpose and allocation of metal ions in various biomolecules. In this study, the interaction of Zn2+, Cd2+ and Ni2+ ions with four peptides containing cysteine triplet motif were studied by potentiometric and …

Coupling of the heme and an internal disulfide bond in human neuroglobin

2004

Neuroglobin displays a hexacoordination His-Fe-His in the absence of external ligands such as oxygen. The observed oxygen affinity therefore depends on the binding rates of both oxygen and the competing distal histidine. Furthermore, the binding properties depend on the presence of an internal disulfide bond. In the case of human neuroglobin, cysteines at positions CD7 and D5 are sufficiently close to form an internal disulfide bond. For cytoglobin, the cysteine residues at positions A7 and GH4 may also form a disulfide bond. Mass spectrometry, ligand binding, and thiol accessibility studies were used to study the role influence of these disulfide bonds. Mutation of specific cysteines, or r…

Electrochemical impedance spectroscopy of polyelectrolyte multilayer modified gold electrodes: influence of supporting electrolyte and temperature.

2005

Electrochemical impedance spectroscopy and cyclic voltammetry are employed to characterize poly(styrenesulfonate)/poly(allylamine hydrochloride) multilayers assembled onto cysteamine-modified gold surfaces. The influence of the supporting electrolyte and temperature on the impedance response is studied because of both its practical interest and the need to test further the capillary membrane model recently developed by Barreira et al. [J. Phys. Chem. B 2004, 108, 17973]. The results obtained are interpreted quite satisfactorily in terms of this model, thus providing additional support to its usefulness for the description of ionic transport through polyelectrolyte multilayers. It is observe…

Preliminary Results of ERAS Protocol in a Single Surgeon Prospective Case Series

2022

Background and Objectives: The aim was to compare the intra and postoperative outcomes between the Enhanced Recovery After Surgery (ERAS) protocol versus the standard of care protocol (SCP) in patients who underwent radical cystectomy performed by a single surgeon. Materials and Methods: A retrospective comparative study was conducted including patients who underwent radical cystectomy from 2017 to 2020. Length of stay (LOS), incidence of ileus, early postoperative complications, and number of re-hospitalizations within 30 days were considered as primary comparative outcomes of the study. Results: Data were collected for 91 patients who underwent cystectomy, and 70 and 21 patients followed …

Diagnostic tools for female urethral diverticulum: Current perspectives

2019

Although once considered quite a rare condition in the past, female urethral diverticulum (UD) would now appear to have a higher frequency, perhaps due to greater attention from physicians. To date, there is no agreement on which is the best method for diagnosis of female UD. Traditionally, the approach was based on quite invasive techniques, such as voiding cystourethrography, and double-balloon urethrography, with satisfactory results but relevant limitations. More recent high-resolution imaging techniques, such as 2D-3D ultrasonography (US) and magnetic resonance imaging (MRI) have also been applied in the study of the abnormalities of the female urethra. US had the advantage of the outp…

Urinary Diversion: How Experts Divert

2014

To determine the rates of the available urinary diversion options for patients treated with radical cystectomy for bladder cancer in different settings (pioneering institutions, leading urologic oncology centers, and population based).Population-based data from the literature included all patients (n = 7608) treated in Sweden during the period 1964-2008, from Germany (n = 14,200) for the years 2008 and 2011, US patients (identified from National Inpatient Sample during 1998-2005, 35,370 patients and 2001-2008, 55,187 patients), and from Medicare (n = 22,600) for the years 1992, 1995, 1998, and 2001. After the International Consultation on Urologic Diseases-European Association of Urology In…