A Devastating Neurological Disorder: Anti-Dipeptidyl-Peptidase-Like Protein 6 (DPPX) Encephalitis Causing Rapidly Progressive Dementia.

Rapidly progressive dementia (RPD) is caused by a heterogeneous group of neurological disorders, and the prototype is Creutzfeldt-Jakob disease (CJD). However, treatable causes including autoimmune encephalitis are often underrecognized and undertreated. A 72-year-old female patient was admitted with a 10-month history of rapidly progressive cognitive decline, visual hallucinations, paranoid behavior, diarrhea, and an 18-kg unintentional weight loss.

Targeting undruggable carbohydrate recognition sites through focused fragment library design.

Carbohydrate-protein interactions are key for cell-cell and host-pathogen recognition and thus, emerged as viable therapeutic targets. However, their hydrophilic nature poses major limitations to the conventional development of drug-like inhibitors. To address this shortcoming, four fragment libraries were screened to identify metal-binding pharmacophores (MBPs) as novel scaffolds for inhibition of Ca-dependent carbohydrate-protein interactions.

Targeting the Central Pocket of the Pseudomonas aeruginosa Lectin LecA.

Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate-binding proteins are central to the initial and later persistent infection processes, i. e.

Case Report: Amphiphysin Antibody-Associated Stiff-Limb Syndrome and Myelopathy: An Unusual Presentation of Breast Cancer in an Elderly Woman.

Paraneoplastic stiff-limb syndrome (SLS) is a rare manifestation of underlying malignancy and could have distinctive features different from the classic stiff-person syndrome (SPS). We present a case of anti-amphiphysin antibody (Ab)-associated paraneoplastic SLS, in an 83-year-old woman with invasive ductal carcinoma of the breast. She presented with stiffness, painful spasms of the distal legs, and asymmetrical fixed posturing of the foot.

Druggable Allosteric Sites in β-Propeller Lectins.

Carbohydrate-binding proteins (lectins) are auspicious targets in drug discovery to combat antimicrobial resistance; however, their non-carbohydrate drug-like inhibitors are still unavailable. Here, we present a druggable pocket in a β-propeller lectin BambL from Burkholderia ambifaria as a potential target for allosteric inhibitors. This site was identified employing F NMR fragment screening and a computational pocket prediction algorithm SiteMap.

Automated Glycan Assembly of F-labeled Glycan Probes Enables High-Throughput NMR Studies of Protein-Glycan Interactions.

Protein-glycan interactions mediate important biological processes, including pathogen host invasion and cellular communication. Herein, we showcase an expedite approach that integrates automated glycan assembly (AGA) of F-labeled probes and high-throughput NMR methods, enabling the study of protein-glycan interactions. Synthetic Lewis type 2 antigens were screened against seven glycan binding proteins (GBPs), including DC-SIGN and BambL, respectively involved in HIV-1 and lung infections in immunocompromised patients, confirming the preference for fucosylated glycans (Le , H type 2, Le ).

Gabapentin-Induced Myokymia: A Case Report.

Background: Gabapentin is a commonly used medication for neuropathic pain and epilepsy that is prescribed by a wide range of medical specialties. Adverse effects including asterixis and myoclonus have been described in patients with chronic kidney disease, but myokymia has not been previously reported.

Case Presentation: A 69-year-old man with a history of traumatic brain injury, peripheral neuropathy, amnesia, and posttraumatic stress disorder presented to the hospital after multiple falls attributed to acute onset muscle spasms.

Non-Carbohydrate Glycomimetics as Inhibitors of Calcium(II)-Binding Lectins.

Because of the antimicrobial resistance crisis, lectins are considered novel drug targets. Pseudomonas aeruginosa utilizes LecA and LecB in the infection process. Inhibition of both lectins with carbohydrate-derived molecules can reduce biofilm formation to restore antimicrobial susceptibility.

From Pyrazolones to Azaindoles: Evolution of Active-Site SHP2 Inhibitors Based on Scaffold Hopping and Bioisosteric Replacement.

The tyrosine phosphatase SHP2 controls the activity of pivotal signaling pathways, including MAPK, JAK-STAT, and PI3K-Akt. Aberrant SHP2 activity leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. SHP2 signaling was recently linked to drug resistance against cancer medications such as MEK and BRAF inhibitors.

A Rare Case of Disseminated Coccidioidomycosis Presenting as Brachial Plexopathy.

Coccidioidomycosis, a fungal infection caused by inhaling spores of /, is endemic to the southwestern states of the United States, Northern Mexico and some parts of Central and South America. It is primarily a pulmonary infection with less than 0.5% of symptomatic cases showing dissemination.

Protein-observed 19F NMR of LecA from Pseudomonas aeruginosa.

The carbohydrate-binding protein LecA (PA-IL) from Pseudomonas aeruginosa plays an important role in the formation of biofilms in chronic infections. Development of inhibitors to disrupt LecA-mediated biofilms is desired but it is limited to carbohydrate-based ligands. Moreover, discovery of drug-like ligands for LecA is challenging because of its weak affinities.

The 3F Library: Fluorinated Fsp -Rich Fragments for Expeditious F NMR Based Screening.

Fragment-based drug discovery (FBDD) is a popular method in academia and the pharmaceutical industry for the discovery of early lead candidates. Despite its wide-spread use, the approach still suffers from laborious screening workflows and a limited diversity in the fragments applied. Presented here is the design, synthesis, and biological evaluation of the first fragment library specifically tailored to tackle both these challenges.

Co-occurrence of multiple sclerosis and myasthenia gravis: A case report and review of immunological theories.

Autoimmune mechanisms are implicated in both myasthenia gravis (MG) and multiple sclerosis (MS), and hypothesis of a common immunological mechanism of pathogenesis is supported by the fact that this rare combination of the two diseases occurs more frequently than expected by random association. Although MS is primarily mediated by T lymphocytes and MG primarily involves the destruction of the neuromuscular junction by antibodies, there are evidences that support both cell-mediated and humoral immunity are involved in the pathogenesis of both diseases. Different studies have shown dysfunction of T cells as well as B cells involved in the pathogenesis of both disorders.

Brachial Plexopathies: Update on Treatment.

Purpose Of Review: Brachial plexopathies (BPs) are a heterogeneous group of diseases which can profoundly affect person's function and quality of life. This review targets current approaches to treatment of different BP types.

Recent Findings: Although there are multiple BP etiologies, non-traumatic causes are particularly unrecognized by clinicians, leading to misdiagnoses and delay in appropriate therapies.

Stereoselective Synthesis of Fluorinated Galactopyranosides as Potential Molecular Probes for Galactophilic Proteins: Assessment of Monofluorogalactoside-LecA Interactions.

The replacement of hydroxyl groups by fluorine atoms on hexopyranoside scaffolds may allow access to invaluable tools for studying various biochemical processes. As part of ongoing activities toward the preparation of fluorinated carbohydrates, a systematic investigation involving the synthesis and biological evaluation of a series of mono- and polyfluorinated galactopyranosides is described. Various monofluorogalactopyranosides, a trifluorinated, and a tetrafluorinated galactopyranoside have been prepared using a Chiron approach.

Human CD22 Inhibits Murine B Cell Receptor Activation in a Human CD22 Transgenic Mouse Model.

CD22, a sialic acid-binding Ig-type lectin (Siglec) family member, is an inhibitory coreceptor of the BCR with established roles in health and disease. The restricted expression pattern of CD22 on B cells and most B cell lymphomas has made CD22 a therapeutic target for B cell-mediated diseases. Models to better understand how in vivo targeting of CD22 translates to human disease are needed.

Identification of Multiple Druggable Secondary Sites by Fragment Screening against DC-SIGN.

DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site.

Intradomain Allosteric Network Modulates Calcium Affinity of the C-Type Lectin Receptor Langerin.

Antigen uptake and processing by innate immune cells is crucial to initiate the immune response. Therein, the endocytic C-type lectin receptors serve as pattern recognition receptors, detecting pathogens by their glycan structures. Herein, we studied the carbohydrate recognition domain of Langerin, a C-type lectin receptor involved in the host defense against viruses such as HIV and influenza as well as bacteria and fungi.