The opportunistic fungal pathogen Candida albicans is a part of the normal flora but it also causes systemic candidiasis if reaches bloodstream. Upon being phagocytized by macrophages, an important component innate immunity, C. rapidly upregulates set arginine biosynthetic genes. Arginine, urea, and CO2 induced hyphae in density-dependent manner wild-type, cph1/cph1, rim101/rim101 strains not efg1/efg1 or cph1/cph1 strains. Arginase (Car1p) converts to which turn degraded urea amidolyase...

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer's disease (AD). 90-kDa heat shock (Hsp90) chaperone system affects accumulation these toxic species, can be modulated with Hsp90 inhibitors. However, many inhibitors are not blood-brain barrier-permeable, and several present associated toxicities. Here, we find cochaperone, activator ATPase homolog 1 (Aha1), dramatically...

ABSTRACT Colonization by the fungal pathogen Candida albicans varies significantly, depending upon pH and availability of oxygen. Because our interest in extracellular molecules as potential quorum-sensing molecules, we examined physiological conditions which regulate production aromatic alcohols, i.e., phenethyl alcohol, tyrosol, tryptophol. The these fusel oils has been well studied for Saccharomyces cerevisiae . Our data show that alcohol yields C. are determined growth conditions. These...

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both and cytoplasmic microtubules. During SPB duplication, newly formed inserted into membrane. mechanism of insertion poorly understood but likely involves action integral membrane proteins to mediate changes itself, such as fusion inner outer membranes. Analysis functional domains SUN protein component Mps3 revealed most regions are not essential for growth or duplication...

Secondary metabolites are well known for their ability to impede other microorganisms. Reanalysis of a screen natural products using the Caenorhabditis elegans-Candida albicans infection model identified twelve microbial secondary capable conferring an increase in survival infected nematodes. In this screen, two compound treatments highest rates were members epipolythiodioxopiperazine (ETP) family fungal metabolites, acetylgliotoxin and derivative hyalodendrin. The abundance indentified...

Biofilms of Candida albicans include both yeast cells and hyphae. Prior studies indicated that a zap1Δ/Δ mutant, defective in zinc regulator Zap1, has increased accumulation biofilms. This altered yeast-hypha balance may arise from internal regulatory alterations or an effect on the production diffusible quorum-sensing (QS) molecules. Here, we develop biosensor reporter strains express yeast-specific YWP1-RFP hypha-specific HWP1-RFP, along with constitutive TDH3-GFP normalization standard....

A mild and greener protocol was developed to synthesize substituted quinazolinones dihydroquinazolinones<italic>via</italic>deep eutectic solvent mediated cyclization with aliphatic, aromatic, heteroaromatic aldehydes in good excellent yields.

Abstract Transient self‐assembling systems often suffer from accumulation of chemical wastes that interfere with the formation pristine self‐assembled products in subsequent cycles. Herein, we report transient crystallization a cucurbit[8]uril‐based host‐guest complex, preventing wastes. Base‐catalyzed thermal decarboxylation trichloroacetic acid chemically fuels process dissolves crystals, and produces volatile are spontaneously removed solution. With such self‐clearance process, no...

In the present work, we demonstrate a regioselective [2 + 2 2] cyclotrimerization of 1,3-diynes catalyzed by Ni0 to provide hexasubstituted benzenes (HSBs). HSBs have significant applications as functional materials and pharmaceuticals. The protocol exhibited remarkable versatility, transforming with diverse alkyl, aryl, heterocyclic groups corresponding HSBs. With help control experiments density theory (DFT), mechanism reaction origin regioselectivity were elucidated.

Glucose regulated protein 94 kDa, Grp94, is the endoplasmic reticulum (ER) localized isoform of heat shock 90 (Hsp90) that responsible for trafficking and maturation toll-like receptors, immunoglobulins, integrins. As a result, Grp94 has emerged as therapeutic target to disrupt cellular communication, adhesion, tumor proliferation, potentially with fewer side effects compared pan-inhibitors all Hsp90 isoforms. Although, N-terminal ATP binding site highly conserved among four isoforms, recent...

Herein we report a facile transformation of hydroxylated cucurbit[n]uril (CB[n], n = 6 and 7) to other functionality-conjugated CB[n]s by nucleophilic substitution the hydroxyl group with wide range nitriles alcohols. The reaction proceeds efficiently via generation superelectrophilic carbocation on CB framework from under superacidic conditions. One resulting CB[n] derivatives reactive functionality, monocarboxylated CB[7], is conjugated an enzyme (horseradish peroxidase, HRP) amide...

Candida albicans causes candidiasis, secretes farnesol, and switches from yeast to hyphae escape macrophages after phagocytosis. However, before escape, may respond C. albicans' pathogen-associated molecular patterns (PAMPs) through toll-like receptor 2 (TLR2) dectin-1 receptors by expressing cytokines involved in adaptive immunity, inflammation, immune regulation. Therefore, the RAW264.7 macrophage line were challenged with preparations of live wild-type cells, heat-killed a mutant...

Human Hsp90 isoforms are molecular chaperones that often up-regulated in malignances and represent a primary target for inhibitors undergoing clinical evaluation. Hsp90α is stress-inducible isoform of plays significant role apoptosis metastasis. Though secreted into the extracellular space under metastatic conditions, its cancer biology poorly understood. We report associates with Aha1 co-chaperone found this complex to localize secretory vesicles at leading edge migrating cells. Knockdown...

The 90-kDa heat-shock protein (Hsp90) assists in the proper folding of numerous mutated or overexpressed signal transduction proteins that are involved cancer. Inhibiting Hsp90 consequently is an attractive strategy for cancer therapy as concomitant degradation multiple oncoproteins may lead to effective antineoplastic agents. Here we report a novel C-terminal inhibitor, designated KU675, exhibits potent antiproliferative and cytotoxic activity along with client without induction response...

This study has paved a new route to achieve <italic>in situ</italic> reversible tuning of chemical interface damping (CID) in the same gold nanorod (AuNR) and investigate CID process using cucurbituril (CB)-based host–guest chemistry with various guest molecules single AuNRs.

The Saccharomyces cerevisiae SUN-domain protein Mps3 is required for duplication of the yeast centrosome-equivalent organelle, spindle pole body (SPB), and it involved in multiple aspects nuclear organization, including telomere tethering gene silencing at membrane, establishment sister chromatid cohesion, repair certain types persistent DNA double-stranded breaks. How these diverse SUN functions are regulated unknown. Here we show that N-terminus a substrate acetyltransferase Eco1/Ctf7...

Abstract Transient self‐assembling systems often suffer from accumulation of chemical wastes that interfere with the formation pristine self‐assembled products in subsequent cycles. Herein, we report transient crystallization a cucurbit[8]uril‐based host‐guest complex, preventing wastes. Base‐catalyzed thermal decarboxylation trichloroacetic acid chemically fuels process dissolves crystals, and produces volatile are spontaneously removed solution. With such self‐clearance process, no...

Novobiocin is a natural product that binds the Hsp90 C-terminus and manifests inhibitory activity. Structural investigations on novobiocin led to development of both anti-cancer neuroprotective agents. The varied pharmacological activity manifested by these analogs prompted investigation structure–function studies identify contradictory effects, which revealed modifications amide side chain produce either or Compounds exhibit contain short alkyl cycloalkyl chain. In contrast, agents five...

Abstract Palladium‐catalyzed cascade cyclization received much attention in organic synthesis due to its efficiency and rapid transformation of simple starting materials into complex molecular skeletons. Celebrating the 10 th year prestigious Nobel prize for palladium chemistry, we witness it still proceeds strong over other transition metals versatility. Cascade reactions contemporary reduced cost time through careful design. It has emerged as first choice, a powerful tool multiple bond...

Here, we report a general copper-catalyzed C(sp3) carboboration of 1,3-diynes, providing access to an array tetra-substituted boryl enynes in regioselective manner. All four positions enyne can be efficiently manipulated using this methodology. The reaction was smoothly applied the conjugation complex bioactive molecules scaffold. Cross-coupling reactions were carried out with boron end groups on densely substituted 1,3-enynes, opening avenues for modular synthesis highly functionalized...

The total synthesis of alkaloid cruciferane is performed in three steps with an overall yield 60.3%.

This paper presents the protoboration of 1,3-diynes as a platform for iterative functionalization various groups on enynes and dienes. Synthetic approaches to targets with high complexity are directed toward using small, modular building blocks similar "Lego" construction chemistry automated synthesis. Organoboron compounds currently in spotlight achieving these goals. Here, we report an operationally simple, regioselective mixed diboron reagent Cu(I)/phosphine catalyst provide...