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1.
J Pharm Bioallied Sci ; 16(Suppl 1): S880-S882, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595618

ABSTRACT

Background: This study compares the effectiveness of laser-assisted periodontal therapy (LAPT) to conventional scaling and root planing (SRP) in the treatment of periodontal disease. Materials and Methods: Patients with periodontal disease were divided into two groups. One group received LAPT, while the other group underwent conventional SRP. The periodontal parameters, including pocket depth (PD) and clinical attachment level (CAL), were measured before and after the treatments. The data were statistically analyzed using appropriate methods. Results: After the treatments, the LAPT group showed a mean reduction in PD of 2.5 mm, while the conventional SRP group had a mean reduction of 2.0 mm. Additionally, the laser group demonstrated a mean improvement in CAL of 1.8 mm, whereas the conventional group showed an improvement of 1.3 mm. These differences were statistically significant (P < 0.05). Conclusion: The findings of this study suggest that LAPT may be more effective in reducing PD and improving CAL compared with conventional SRP in the treatment of periodontal disease.

3.
Mediterr J Rheumatol ; 34(1): 101-104, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37223603

ABSTRACT

Systemic lupus erythematosus may present with fever, and it is a challenge to attribute fever to a particular cause. Very rarely it can be due to hyperthyroidism. Thyroid storm is a medical emergency causing unrelenting pyrexia. Here we report a case of a young female who first presented as fever of unknown origin (FUO), was subsequently diagnosed as neuropsychiatric lupus, and in whom the cause of unrelenting high fever, which did not respond to adequate immunosuppression to quell disease activity, was documented to be thyroid storm after excluding all other causes such as infection and malignancy. To our knowledge, this is the first case of this kind reported in literature, although cases of thyrotoxicosis preceding or following the diagnosis of lupus is known. Her fever resolved after starting antithyroid drugs and beta blockers.

4.
J Indian Prosthodont Soc ; 23(2): 112-118, 2023.
Article in English | MEDLINE | ID: mdl-37102535

ABSTRACT

Aim: One of the main factors responsible for the development of Candida albicans on the surface of denture is improper maintenance of dentures. Denture hygiene can be achieved by regular cleansing of dentures using an appropriate denture cleanser. The aim of the study is to evaluate the antifungal efficacy of commercially available denture cleanser and the extract of Turbinaria conoides seaweed against C. albicans adherent to the surface of denture base resin. Settings and Design: This was an in vitro experimental study. Materials and Methods: Twenty-four Acrylic resin samples of dimension 10-mm radius and 2-mm thickness was randomly divided into two groups. The denture base resin was coated with C. albicans. The colonies present on the surface of each denture base resin were evaluated by serial dilution method. Group A was treated with commercially available denture cleanser and Group B was treated with extract of seaweed T. conoides. The colonies were then evaluated using serial dilution. Statistical Analysis Used: The colony count values obtained by serial dilution were tabulated. These values were statistically analysed using t-test. Results: Reduction of colony count is more in T. conoides than commercially available Fittydent; the difference was statistically significant with a mean difference of 65 at dilution 10-2 and 29.25 at dilution 10-3 using t-test with P < 0.001. Conclusion: Within the limitations of this in vitro study, it was proved that the extract of T. conoides seaweed and commercially available denture cleanser Fittydent was effective in reducing the colony count of C. albicans. T. conoides seaweed is statistically significant than commercially available Fittydent.


Subject(s)
Antifungal Agents , Denture Cleansers , Phaeophyceae , Plant Extracts , Acrylic Resins , Antifungal Agents/pharmacology , Candida albicans , Denture Bases/microbiology , Phaeophyceae/chemistry , Plant Extracts/pharmacology , Seaweed , Microbial Sensitivity Tests
5.
Cureus ; 15(1): e34388, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36874738

ABSTRACT

Xanthogranulomatous pyelonephritis (XPG) is a known clinical entity; however, the further progression of this inflammatory pathology to adjacent organs, including the ureter, bladder and urethra, is extremely rare. Xanthogranulomatous inflammation of the ureter is a chronic inflammatory state where foamy macrophages are seen in the lamina propria along with multinucleated giant cells and lymphocytes forming a granulomatous inflammation, which is benign. Based on its appearance on computed tomography (CT) scan images, it can easily be misidentified as a malignant mass, and the patient can be subjected to surgery that can lead to complications. Here we present a case of an elderly male with a known case of chronic kidney disease with uncontrolled type 2 diabetes mellitus who presented with fever and dysuria. Upon further radiological investigations, the patient had underlying sepsis and was seen to have a mass involving the right ureter and inferior vena cava. Upon biopsy and histopathology, he was diagnosed with xanthogranulomatous ureteritis (XGU). The patient underwent further treatment and was followed up.

6.
Cureus ; 15(1): e33754, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36793837

ABSTRACT

The Coronavirus disease pandemic is an evolving disease with myriad presentations and sequelae. Multisystem inflammatory syndrome in adults (MIS-A) can affect various organ systems, including cardiovascular, gastrointestinal, and neurologic systems, with fever and abnormally increased inflammatory markers without significant respiratory affection. This is a well-known complication in children (MIS-C). Validated clinical criteria are used to diagnose this condition. Long-term sequelae of MIS-A are unclear and underreported. Here, we describe a case of Post-COVID-19 MIS-A who presented with cardiac dysfunction, hepatitis, and acute kidney injury and recovered well with steroids. He was left with persistent cardiomyopathy and thyroiditis with hypothyroidism which to date has not fully recovered. This case emphasizes that the sequelae of COVID-19 and its pathophysiology are not fully understood, and more research is needed to predict and prevent the same.

7.
Radiat Prot Dosimetry ; 199(2): 164-170, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36515393

ABSTRACT

Patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) is essential for complex radiotherapy treatment as it involves complex intensity modulation and high-dose gradient regions. IMRT QA was performed by point dose verification and two-dimensional (2D) dose distribution measurement using gamma method. Calibrated External Beam Therapy 3 (EBT3) film was used for point dose and pre-treatment verification of 10 IMRT plans, five complex Head and Neck (HN) and five brain cases. The gamma passing rate (GPR) was evaluated for 3%/3 mm gamma criteria and compared with 2D array. Isocentre dose was measured for all 10 IMRT plans on EBT3 film. Percentage deviation of point dose measurement from TPS calculated was found 0.4% for brain cases and 2.9% for HN cases. The GPR for 3%/3 mm criteria was obtained higher than 95% for brain and HN cases. Results suggest that film dosimetry is also a reliable verification system for patient-specific IMRT QA as the 2D array.


Subject(s)
Brain Neoplasms , Radiotherapy, Intensity-Modulated , Humans , Radiotherapy, Intensity-Modulated/methods , Radiotherapy Dosage , Brain Neoplasms/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Head , Quality Assurance, Health Care , Radiometry/methods
8.
Front Immunol ; 14: 1285162, 2023.
Article in English | MEDLINE | ID: mdl-38235130

ABSTRACT

Background: Thrombocytopenia is the most notable phenomenon in dengue. Activation status of platelets and interaction of platelets with endothelium contribute towards dengue disease pathogenesis. Platelets are the major cell types known to release extracellular vesicles, especially exosomes in circulation. However, the role of platelet derived exosomes (PLT-EXOs) in endothelial dysfunction during dengue infection remains unknown. Methods: In this study, we recruited 28 healthy subjects and 69 dengue patients categorized as WS- (n=31), WS+ (n=29) and SD (n=9). Platelets were isolated from platelet rich plasma of dengue patients and their activation was assessed by flow cytometry. PLT-EXOs were isolated by ultracentrifugation method. Western blot analyses were performed to characterize the exosomes. Exosome uptake experiment was carried out to see the internalization of exosomes inside endothelial cells (HUVECs). To observe the effect of exosomes on endothelial cells, exosomes were added on HUVECs and expression of adherens and tight junctional proteins were examined by immunofluorescence assay and western blot. Expression levels of vascular injury markers were measured in the culture supernatants of Exosome-HUVEC coculture and sera of dengue patients by MSD-multiplex assay. Results: As compared to healthy subjects, CD41/CD61 expression was significantly reduced (p<0.0001) and CD62p expression was significantly increased (p<0.0001) on platelets in dengue patients. PLT-EXOs isolated from the dengue patients showed higher expression of CD63 and CD9 proteins than the healthy subjects. With in-vitro immunofluorescence assays, we illustrated the internalization of PLT-EXOs by the HUVECs and observed disruption of endothelial cell monolayer integrity in the presence of PLT-EXOs from WS+ and SD patients. Furthermore, the significant reduction in the expressions of ZO-2, VE-Cadherin and CD31 in endothelial cells following exposure to PLT-EXOs from the dengue patients provide direct evidence of PLT-EXOs mediated vascular permeability. PLT-EXOs stimulated the release of inflammatory markers CRP, SAA, sVCAM-1 and sICAM-1 in the supernatants of HUVEC cells. Importantly, significantly higher levels of CRP, sVCAM-1 and sICAM-1 in the sera of severe than mild dengue patients (p<0.0001) suggest their role in disease severity. Conclusions: In summary, our data suggest that PLT-EXOs promote vascular leakage via release of proinflammatory mediators and compromise vascular barrier integrity in dengue patients.


Subject(s)
Dengue , Exosomes , Humans , Exosomes/metabolism , Blood Platelets , Human Umbilical Vein Endothelial Cells/metabolism , Inflammation/metabolism , Dengue/metabolism
9.
J Cutan Aesthet Surg ; 15(3): 288-294, 2022.
Article in English | MEDLINE | ID: mdl-36561407

ABSTRACT

Background: Vitiligo is the most common depigmenting dermatosis causing immense psychosocial concern. When medical therapies fail to cause re-pigmentation, surgical modalities are developed to combat the same in stable vitiligo patients. Here we are comparing two such surgeries: smash skin grafting (SSG) and autologous non-cultured epidermal cell suspension (NCES). Aims and Objectives: The aim of this article is to compare the efficacy of SSG and NCES in re-pigmentation of stable vitiligo and to know the feasibility of both the surgeries. Materials and Methods: It is an open, randomized, and prospective study conducted in dermatology outpatient department at a tertiary care center. Thirty patients with single stable vitiligo lesion were randomized into two groups: 15 each in Group A (SSG) and Group B (NCES). Following the surgery, excimer lamp phototherapy was initiated twice weekly. Patients were followed up till 16 weeks of surgery. Photo-documentation was done every month. Grading was performed for the response in the form of re-pigmentation as excellent (>75%), good (50-75%), fair (25-50%), and poor (<25%). The χ2 test was used to analyze statistical significance. Results: Both the surgeries showed initial specks of re-pigmentation at 10-14 days post-surgery. Excellent response (>75% re-pigmentation) was observed in 10 (66.67%) patients in Group A and 9 (60%) patients in Group B. Both the surgeries showed equal response and uniform texture of re-pigmentation. Conclusion: SSG is equally effective when compared with NCES, in causing re-pigmentation. Also, SSG is simple, easy to perform, faster learning curve, less time-consuming, and cost-effective when compared with NCES.

10.
J Cutan Aesthet Surg ; 15(3): 327-329, 2022.
Article in English | MEDLINE | ID: mdl-36561414

ABSTRACT

Subcutaneous phycomycosis is a rare saprophytic fungal infection. We herein report a case of subcutaneous phycomycosis with stony hard swelling on the chest wall as an unusual site of infection. Diagnosis was made based on the clinical, histopathological, and culture studies. Oral treatment with itraconazole resulted in rapid resolution of lesion.

11.
Dermatol Pract Concept ; 12(4): e2022180, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36534553

ABSTRACT

Introduction: Blister beetle dermatitis (BBD) and herpes zoster (HZ) manifest suddenly with vesicular lesions mimicking each other and progress rapidly. But a lack of definite differentiating criteria yearns the need for better investigating modality. Though histopathology persuades the need, is an invasive procedure, commonly deferred. Thus, dermoscopy, a non-invasive rapid diagnostic tool, can help in differentiating. Objectives: To evaluate different dermoscopic patterns of BBD and HZ to differentiate both and to study dermoscopic features in early and late stages of lesions. Methods: An observational cross-section study conducted in southern India. Nine patients with clinical features suggestive of BBD and HZ were recruited. Lesions were divided arbitrarily into early and late. Dermoscopic examination was performed with handheld dermoscope. Diagnosis was confirmed by skin biopsy and Tzanck smear wherever necessary. Statistical analysis performed using data in terms of frequencies and percentages. Results: Dermoscopy of early BBD lesions showed multiple discrete and confluent yellowish-white structures, brown dots, roundish white globules, gray structures, 'targetoid pattern', brown areas over intense reddish pink background. Late BBD lesions revealed pinkish-white area, reduced gray structures and, dotted and globular vessels. Early HZ lesions showed poly-lobular gray and brown globules, bright pink background, gray globules covered by grayish veil-like structure with gray rim. Late HZ lesions revealed 'solar eclipse' pattern and 'crumpled fabric' patterns. The dermoscopic findings correlated with histopathology. Conclusions: Dermoscopic patterns show peculiar features consistently pertaining to BBD and HZ, thus help in early diagnosis assisting in accurate treatment in both conditions.

12.
Cureus ; 14(10): e30481, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36415371

ABSTRACT

Background Musculoskeletal disorders (MSDs) are one of the most common occupational diseases. MSDs cause an economic burden as they lead to disability, absenteeism, and reduced productivity. Although many risk factors have been associated with the incidence of MSDs, little is known about the predictive factors for the length of MSD-related absenteeism. The study aimed to estimate the prevalence of MSDs among garment factory workers, determine the predictive factors for length of sickness absence, and evaluate the association of these factors with time. Methodology This prospective, observational, community-based study was conducted among garment factory workers. A total of 430 participants were included in the study by multistage sampling to assess the prevalence and factors causing MSDs, followed by a one-year follow-up to analyze the MSD-associated predictors for sickness absence. The data were analyzed using SPSS version 22 (IBM Corp., Armonk, NY, USA). The chi-square test and logistic regression were used to test significance, and Cox regression was used to determine the predictive factors for sickness absence. Results The mean age of the participants was 29.36 years. The 12-month prevalence showed that the most affected region was the lower back (70%), followed by the upper back (40%), with some workers experiencing both. There was a significant relation between MSDs and higher age, low work experience, being overweight, and long work hours (p < 0.05). According to the multivariate analysis, the perceived pain (hazards ratio (HR) = 1.14), perceived physical workload (HR = 1.14), and visiting a specialist 12 months prior to the current absence (HR = 1.68) were significantly associated with a longer sickness absence. Conclusions The lower and upper back were most commonly affected. The predictors for absence revealed that physical work overload and pain perception had a predominant role in the duration of absence. Hence, an ergonomically acceptable workplace with considerate rest periods will help enhance productivity.

13.
Case Rep Dent ; 2022: 3080039, 2022.
Article in English | MEDLINE | ID: mdl-35928397

ABSTRACT

The loss of teeth affects the aesthetics, function (mastication and speech), confidence, mental state, and the overall quality of life of an individual. Aggressive periodontitis is a destructive condition leading to loss of teeth at early stages of the disease. Individuals facing this inevitable condition of losing the teeth and replacement at a younger age experience formidable psychological distress. The prosthodontic procedure when supported with psychotherapeutic interventions can support the patient in accepting the prognosis and treatment. We report the scenario where psychological intervention was provided in a systematic manner adopting the SPIKES protocol for a 42-year-old man presenting with aggressive periodontitis.

14.
Orbit ; 41(3): 321-323, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33736568

ABSTRACT

PURPOSE: The use of prophylactic antibiotics for oculoplastic procedures varies because of a lack of specific guidelines or literature. Comparable studies in clean orbital surgery have shown no proven benefit and its indiscriminate use has been linked to individual harm and rising levels of resistance. We investigated whether avoidance of systemic prophylactic antibiotics in elective lid surgeries increased surgical site infections (SSI). METHODS: We conducted a case-note audit of consecutive anterior ptosis repair and lateral tarsal strip (LTS) surgeries performed with post-operative oral antibiotics (co-amoxiclav or clarithromycin) and topical chloramphenicol ointment, compared to only topical antibiotics. Data on American Society of Anesthesiologists (ASA) status, age and incidence of surgical site infection at 2 weeks follow-up were collected. RESULTS: Of a cohort of 232 patients, 99 patients had combined systemic and topical antibiotics (ptosis n = 49, LTS n = 50) and 133 had topical antibiotics (ptosis n = 83, LTS n = 50). The groups were not significantly different for age (p = .6, t-test) or ASA status (p = .7, chi2 test). Three patients from the combined group required further treatment for SSI compared with two patients from the topical antibiotic group (p = .7 Fisher's exact test). CONCLUSIONS: Avoidance of systemic antibiotic prophylaxis for LTS and anterior ptosis repair procedures was not associated with increased SSI rates. Given that prescriptions of antibiotics carry the risk of side-effects and growing antimicrobial resistance, we feel that our study shows that its routine use in this setting is of no benefit.


Subject(s)
Anti-Bacterial Agents , Antibiotic Prophylaxis , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/methods , Elective Surgical Procedures , Eyelids/surgery , Humans , Surgical Wound Infection/drug therapy , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control
15.
J Magn Reson Imaging ; 55(4): 1060-1081, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34046959

ABSTRACT

Three-dimensional (3D) printing technologies have been increasingly utilized in medicine over the past several years and can greatly facilitate surgical planning thereby improving patient outcomes. Although still much less utilized compared to computed tomography (CT), magnetic resonance imaging (MRI) is gaining traction in medical 3D printing. The purpose of this study was two-fold: 1) to determine the prevalence in the existing literature of using MRI to create 3D printed anatomic models for surgical planning and 2) to provide image acquisition recommendations for appropriate clinical scenarios where MRI is the most suitable imaging modality. The workflow for creating 3D printed anatomic models from medical imaging data is complex and involves image segmentation of the regions of interest and conversion of that data into 3D surface meshes, which are compatible with printing technologies. CT is most commonly used to create 3D printed anatomic models due to the high image quality and relative ease of performing image segmentation from CT data. As compared to CT datasets, 3D printing using MRI data offers advantages since it provides exquisite soft tissue contrast needed for accurate organ segmentation and it does not expose patients to unnecessary ionizing radiation. MRI, however, often requires complicated imaging techniques and time-consuming postprocessing procedures to generate high-resolution 3D anatomic models needed for 3D printing. Despite these challenges, 3D modeling and printing from MRI data holds great clinical promises thanks to emerging innovations in both advanced MRI imaging and postprocessing techniques. EVIDENCE LEVEL: 2 TECHNICAL EFFICATCY: 5.


Subject(s)
Imaging, Three-Dimensional , Models, Anatomic , Humans , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging , Printing, Three-Dimensional , Tomography, X-Ray Computed
16.
J Anaesthesiol Clin Pharmacol ; 37(3): 389-394, 2021.
Article in English | MEDLINE | ID: mdl-34759549

ABSTRACT

BACKGROUND AND AIMS: Caudal epidural and ultrasound-guided ilioinguinal, iliohypogastric nerve (IL/IH) blocks are commonly used regional anesthesia techniques for postoperative analgesia in pediatric inguinal surgeries. Dexmedetomidine as an adjuvant has been proven to prolong the duration of both neuraxial and peripheral nerve blocks. We compared the duration of analgesia provided by local anesthetic (LA) and dexmedetomidine for caudal and IL/IH block for pediatric inguinal surgeries. MATERIAL AND METHODS: Forty-six children undergoing inguinal hernia repair were selected for this randomized double-blind study. After general anesthesia, children received either 0.75 mL.kg-1 of 0.25% bupivacaine with 1 mcg.kg-1 of dexmedetomidine in caudal epidural or 0.25 mL.kg-1 of 0.25% bupivacaine with 1 mcg.kg-1 of dexmedetomidine in IL/IH block. The pain was assessed up to 24 h postoperatively using face, legs, activity, cry, consolability (FLACC) score. For FLACC ≥4, rescue analgesia was provided using 1 µg/kg of intravenous fentanyl, up to 2 h postoperatively and 10 mg/kg of oral ibuprofen between 2 and 24 postoperative hours. The time for first rescue analgesia was taken as the duration of analgesia. RESULTS: There were no significant differences in the pain scores or analgesic utilization between the groups. The duration of analgesia of caudal and IL/IH blocks was similar (720.3 ± 430.1 min and 808.4 ± 453.1 min, respectively). The time taken for the performance of block was significantly higher for caudal compared to IL/IH (547 ± 93 vs. 317 ± 179 s; P < 0.001). CONCLUSION: Both caudal epidural and USG-IL/IH block with dexmedetomidine as additive provide the comparable duration of postoperative analgesia with no significant side effects.

17.
Dermatol Pract Concept ; 11(3): e2021057, 2021 May.
Article in English | MEDLINE | ID: mdl-34123561

ABSTRACT

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) causes extracellular proteinaceous deposits in skin. It is clinically divided into macular amyloidosis, lichen amyloidosis and nodular amyloidosis. Atypical presentations of PLCA make the diagnosis challenging, requiring biopsy to confirm amyloid deposition in the upper papillary dermis. OBJECTIVES: This study used FotoFinder dermoscopy to characterize lichen and macular amyloidosis and correlated the dermoscopic features with histopathological findings. METHODS: This cross-sectional study enrolled patients with a clinical and histopathological diagnosis of PLCA. Dermoscopic examination was performed using the FotoFinder dermoscope, which provides a range of magnification from 20× to 140×. RESULTS: A total of 30 patients were included in the study. Common dermoscopic patterns of MA were white or brown central hubs, and common patterns of LA were white structureless, scar-like areas and central hubs. New dermoscopic findings were a day lily appearance in MA and white rosettes in LA. CONCLUSIONS: Dermoscopy plays a pivotal role in demonstrating characteristic findings of PLCA. These findings were well corelated with histopathology, thus avoiding unnecessary biopsy for arriving at an accurate diagnosis of PLCA.

19.
ChemMedChem ; 16(1): 113-123, 2021 01 08.
Article in English | MEDLINE | ID: mdl-32542998

ABSTRACT

We applied dynamic combinatorial chemistry (DCC) to find novel ligands of the bacterial virulence factor glucosyltransferase (GTF) 180. GTFs are the major producers of extracellular polysaccharides, which are important factors in the initiation and development of cariogenic dental biofilms. Following a structure-based strategy, we designed a series of 36 glucose- and maltose-based acylhydrazones as substrate mimics. Synthesis of the required mono- and disaccharide-based aldehydes set the stage for DCC experiments. Analysis of the dynamic combinatorial libraries (DCLs) by UPLC-MS revealed major amplification of four compounds in the presence of GTF180. Moreover, we found that derivatives of the glucose-acceptor maltose at the C1-hydroxy group act as glucose-donors and are cleaved by GTF180. The synthesized hits display medium to low binding affinity (KD values of 0.4-10.0 mm) according to surface plasmon resonance. In addition, they were investigated for inhibitory activity in GTF-activity assays. The early-stage DCC study reveals that careful design of DCLs opens up easy access to a broad class of novel compounds that can be developed further as potential inhibitors.


Subject(s)
Anti-Bacterial Agents/chemistry , Bacteria/enzymology , Bacterial Proteins/antagonists & inhibitors , Glucosyltransferases/antagonists & inhibitors , Sugars/chemistry , Anti-Bacterial Agents/metabolism , Bacterial Proteins/metabolism , Combinatorial Chemistry Techniques , Drug Discovery , Glucosyltransferases/metabolism , Protein Binding , Small Molecule Libraries/chemistry , Small Molecule Libraries/metabolism , Structure-Activity Relationship , Surface Plasmon Resonance
20.
Chemistry ; 26(64): 14585-14593, 2020 Nov 17.
Article in English | MEDLINE | ID: mdl-32428268

ABSTRACT

Kinetic target-guided synthesis represents an efficient hit-identification strategy, in which the protein assembles its own inhibitors from a pool of complementary building blocks via an irreversible reaction. Herein, we pioneered an in situ Ugi reaction for the identification of novel inhibitors of a model enzyme and binders for an important drug target, namely, the aspartic protease endothiapepsin and the bacterial ß-sliding clamp DnaN, respectively. Highly sensitive mass-spectrometry methods enabled monitoring of the protein-templated reaction of four complementary reaction partners, which occurred in a background-free manner for endothiapepsin or with a clear amplification of two binders in the presence of DnaN. The Ugi products we identified show low micromolar activity on endothiapepsin or moderate affinity for the ß-sliding clamp. We succeeded in expanding the portfolio of chemical reactions and biological targets and demonstrated the efficiency and sensitivity of this approach, which can find application on any drug target.


Subject(s)
Drug Delivery Systems , Chemistry Techniques, Synthetic , Kinetics
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