Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rational Design of Phe-BODIPY Amino Acids as Fluorogenic Building Blocks for Peptide-Based Detection of Urinary Tract Candida Infections.

ABSTRACT: Fungal infections caused by Candida species are among the most prevalent in hospitalized patients. However, current methods for the detection of Candida fungal cells in clinical samples rely on time-consuming assays that hamper rapid and reliable diagnosis. Herein, we describe the rational development of new Phe-BODIPY amino acids as small fluorogenic building blocks and their application to generate fluorescent antimicrobial peptides for rapid labelling of Candida cells in urine. We have used computational methods to analyse the fluorogenic behaviour of BODIPY-substituted aromatic amino acids and performed bioactivity and confocal microscopy experiments in different strains to confirm the utility and versatility of peptides incorporating Phe-BODIPYs. Finally, we have designed a simple and sensitive fluorescence-based assay for the detection of Candida albicans in human urine samples.

SUBMITTER: Mendive-Tapia L

PROVIDER: S-EPMC9305947 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Rational selection of building blocks for the assembly of bispecific antibodies.

Project description:Bispecific antibodies, engineered to recognize two targets simultaneously, demonstrate exceptional clinical potential for the therapeutic intervention of complex diseases. However, these molecules are often composed of multiple polypeptide chains of differing sequences. To meet industrial scale productivity, enforcing the correct quaternary assembly of these chains is critical. Here, we describe Chain Selectivity Assessment (CSA), a high-throughput method to rationally select parental monoclonal antibodies (mAbs) to make bispecific antibodies requiring correct heavy/light chain pairing. By deploying CSA, we have successfully identified mAbs that exhibit a native preference toward cognate chain pairing that enables the production of hetero-IgGs without additional engineering. Furthermore, CSA also identified rare light chains (LCs) that permit positive binding of the non-cognate arm in the common LC hetero-IgGs, also without engineering. This rational selection of parental mAbs with favorable developability characteristics is critical to the successful development of bispecific molecules with optimal manufacturability properties.

| S-EPMC7808324 | biostudies-literature

New preorganized γ-amino acids as foldamer building blocks.

Project description:An asymmetric synthesis of two new diastereomeric γ-amino acids is described. Both molecules contain a cyclohexyl ring to limit conformational flexibility about the Cα-Cβ bond; they differ in having cis vs trans stereochemistry on the ring. Residues derived from the cis γ isomer are shown to support helical secondary structures in α/γ-peptide oligomers.

| S-EPMC3445736 | biostudies-literature

Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors.

Project description:Carbonic anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life, classified into seven genetically different families (α⁻θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO₂), generating bicarbonate (HCO₃-) and protons (H⁺). Fifteen isoforms of human CA (hCA I⁻XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) have been used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

| S-EPMC6027070 | biostudies-literature

Diverse N-Substituted Azole-Containing Amino Acids as Building Blocks for Cyclopeptides.

Project description:The preparation of 16 oxazole- or thiazole-containing amino esters bearing a wide array of N-substitution is reported. These were accessed in 40-92% yield via an AgClO4-promoted substitution reaction between a primary amine and a chloromethyl-functionalized thiazole or oxazole. These new synthetic building blocks will be useful for the preparation of new cyclopeptide analogues bearing heterocyclic backbone modifications. Four macrocyclic N-substituted oligoamides that include thiazole or oxazole heterocycles were obtained, following cyclooligomerization reactions of azole-modified N-substituted amino acids.

| S-EPMC6977196 | biostudies-literature

Reverse C-glycosidase reaction provides C-nucleotide building blocks of xenobiotic nucleic acids.

Project description:C-Analogues of the canonical N-nucleosides have considerable importance in medicinal chemistry and are promising building blocks of xenobiotic nucleic acids (XNA) in synthetic biology. Although well established for synthesis of N-nucleosides, biocatalytic methods are lacking in C-nucleoside synthetic chemistry. Here, we identify pseudouridine monophosphate C-glycosidase for selective 5-β-C-glycosylation of uracil and derivatives thereof from pentose 5-phosphate (D-ribose, 2-deoxy-D-ribose, D-arabinose, D-xylose) substrates. Substrate requirements of the enzymatic reaction are consistent with a Mannich-like addition between the pyrimidine nucleobase and the iminium intermediate of enzyme (Lys166) and open-chain pentose 5-phosphate. β-Elimination of the lysine and stereoselective ring closure give the product. We demonstrate phosphorylation-glycosylation cascade reactions for efficient, one-pot synthesis of C-nucleoside phosphates (yield: 33 - 94%) from unprotected sugar and nucleobase. We show incorporation of the enzymatically synthesized C-nucleotide triphosphates into nucleic acids by RNA polymerase. Collectively, these findings implement biocatalytic methodology for C-nucleotide synthesis which can facilitate XNA engineering for synthetic biology applications.

| S-EPMC7722734 | biostudies-literature

Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications.

Project description:This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely distributed in nature and are known to enhance the stability of specific secondary structures and/or biological function. Contrary to the ubiquitous DNA-encoded amino acids, the structure and function of these residues are not fully understood. Here, results from experimental and molecular modelling approaches are gathered to classify several classes of non-canonical amino acids according to their ability to induce specific secondary structures yielding different biological functions and improved stability. Regarding side-chain modifications, symmetrical and asymmetrical α,α-dialkyl glycines, Cα to Cα cyclized amino acids, proline analogues, β-substituted amino acids, and α,β-dehydro amino acids are some of the non-canonical representatives addressed. Backbone modifications were also examined, especially those that result in retro-inverso peptidomimetics and depsipeptides. All this knowledge has an important application in the field of peptidomimetics, which is in continuous progress and promises to deliver new biologically active molecules and new materials in the near future.

| S-EPMC10296201 | biostudies-literature

Tamm-Horsfall Protein Protects the Urinary Tract against <i>Candida albicans</i>.

Project description:Urinary tract infections (UTIs) caused by the human fungal pathogen Candida albicans and related species are prevalent in hospitalized patients, especially those on antibiotic therapy, with indwelling catheters, or with predisposing conditions such as diabetes or immunodeficiency. Understanding of key host defenses against Candida UTI is critical for developing effective treatment strategies. Tamm-Horsfall glycoprotein (THP) is the most abundant urine protein, with multiple roles in renal physiology and bladder protection. THP protects against bacterial UTI by blocking bacterial adherence to the bladder epithelium, but its role in defense against fungal pathogens is not yet described. Here we demonstrate that THP restricts colonization of the urinary tract by C. albicans THP binds to C. albicans hyphae, but not the yeast form, in a manner dependent on fungal expression of the Als3 adhesion glycoprotein. THP directly blocks C. albicans adherence to bladder epithelial cells in vitro, and THP-deficient mice display increased fungal burden in a C. albicans UTI model. This work outlines a previously unknown role for THP as an essential component for host immune defense against fungal urinary tract infection.

| S-EPMC6246913 | biostudies-literature

Investigating Candida glabrata Urinary Tract Infections (UTIs) in Mice Using Bioluminescence Imaging.

Project description:Urinary tract infections (UTIs) are quite common and mainly caused by bacteria such as Escherichia coli. However, when patients have urinary catheters, fungal infections comprise up to 15% of these types of infections. Moreover, fungal UTIs have a high mortality, due to rapid spreading of the fungi to the kidneys. Most fungal UTIs are caused by Candida species, among which Candida albicans and Candida glabrata are the most common. C. glabrata is an opportunistic pathogenic yeast, phylogenetically quite close to Saccharomyces cerevisiae. Even though it is commonly isolated from the urinary tract and rapidly acquires resistance to antifungals, its pathogenesis has not been studied extensively in vivo. In vivo studies require high numbers of animals, which can be overcome by the use of non-invasive imaging tools. One such tool, bioluminescence imaging, has been used successfully to study different types of C. albicans infections. For C. glabrata, only biofilms on subcutaneously implanted catheters have been imaged using this tool. In this work, we investigated the progression of C. glabrata UTIs from the bladder to the kidneys and the spleen. Furthermore, we optimized expression of a red-shifted firefly luciferase in C. glabrata for in vivo use. We propose the first animal model using bioluminescence imaging to visualize C. glabrata in mouse tissues. Additionally, this UTI model can be used to monitor antifungal activity in vivo over time.

| S-EPMC8538756 | biostudies-literature

A BODIPY-Based Fluorogenic Probe for Specific Imaging of Lipid Droplets.

Project description:We developed an easily accessible boron-dipyrromethene (BODIPY)-based fluorogenic probe, which we named LD-TB. This probe emits bright fluorescence in oil; when compared with aqueous solution, a significant enhancement of fluorescence brightness is observed. Cellular experiments confirmed that the probe stains the lipid droplets (LDs) specifically in both live and fixed cells, providing background-free images. Compared with Nile Red dye, a commonly used LD marker, LD-TB showed superior photostability. The sharp absorption and emission bands enable its multicolor imaging with blue and green probes. Importantly, the probe has proved to have low toxicity and is compatible with cell fixation. Our research provides a promising new fluorogenic probe for specific imaging of LDs.

| S-EPMC7040634 | biostudies-literature

Caged O-phosphorothioyl amino acids as building blocks for Fmoc-based solid phase peptide synthesis.

Project description:The synthesis of 1-(2-nitrophenylethyl) caged O-phosphorothioylserine, -threonine and -tyrosine derivatives is reported. These amino acid building blocks can be directly incorporated into peptides by Fmoc-based solid phase synthesis as their pentafluorophenyl esters or as symmetric anhydrides. Upon irradiation with UV light, the thiophosphate group, representing a hydrolysis resistant phosphate analog, is revealed.

| S-EPMC2699315 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data