A5022730708- Nanoplatforms for cancer theranostics
- Photodynamic Therapy Research Studies
- Prostate Cancer Treatment and Research
- Click Chemistry and Applications
- Cancer-related gene regulation
- Antimicrobial Peptides and Activities
- Radiopharmaceutical Chemistry and Applications
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- Protein Hydrolysis and Bioactive Peptides
- Chemical Synthesis and Analysis
- Pneumocystis jirovecii pneumonia detection and treatment
- Peptidase Inhibition and Analysis
- Polydiacetylene-based materials and applications
- Bladder and Urothelial Cancer Treatments
- Neuroscience and Neuropharmacology Research
- Nigella sativa pharmacological applications
- Antimicrobial agents and applications
- Monoclonal and Polyclonal Antibodies Research
- Malaria Research and Control
- Supramolecular Self-Assembly in Materials
- HIV/AIDS drug development and treatment
- Enzyme Catalysis and Immobilization
Radboud University Nijmegen
2009-2024
Radboud Institute for Molecular Life Sciences
2023
Radboud University Medical Center
2023
Incomplete resection of prostate cancer (PCa) occurs in 15%-50% PCa patients. Disease recurrence negatively impacts oncological outcome. The use radio-, fluorescent-, or photosensitizer-labeled ligands to target the prostate-specific membrane antigen (PSMA) has become a well-established method for detection and treatment PCa. Methods: Here, we developed characterized multimodal [111In]In-DOTA(GA)-IRDye700DX-PSMA ligands, varying their molecular composition, intraoperative radiodetection,...
The first generation ligands for prostate-specific membrane antigen (PSMA)-targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we developed three new photosensitizer-based dual-labeled PSMA crucial modification existing ligand backbone structures (PSMA-1007/PSMA-617) multimodal imaging targeted PDT PCa.Various were synthesized using solid-phase chemistry provided with a DOTA chelator 111In...
Abstract Histone lysine methyltransferases (KMTs) are biomedically important epigenetic enzymes that catalyze the transfer of methyl group from S -adenosylmethionine to lysine’s nucleophilic ε-amino in histone tails and core histones. Understanding chemical basis KMT catalysis is for discerning its complex biology disease, structure-function relationship, designing specific inhibitors with therapeutic potential. Here we examine peptides, which possess simplest analogs different character, as...
Incomplete resection of prostate cancer (PCa) results in increased risk disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting DOTA chelator for 111In labeling and fluorophore/photosensitizer IRDye700DX (PSMA-N064). evaluated the efficacy PSMA-tPDT using PSMA-N064 cell viability assays, mouse xenograft model an ex vivo...
Strain-promoted azide–alkyne cycloaddition (SPAAC) is a straightforward and multipurpose conjugation strategy. The use of SPAAC to link different functional elements prostate-specific membrane antigen (PSMA) ligands would facilitate the development modular platform for PSMA-targeted imaging therapy prostate cancer (PCa). As first proof concept chemistry platform, we synthesized characterized four dual-labeled PSMA intraoperative radiodetection fluorescence PCa. Ligands were using solid-phase...
Bacterial biofilms represent an escalating global health concern with the proliferation of drug resistance and hospital-acquired infections annually. Numerous strategies are under exploration to combat preempt development antibacterial resistance. Among these, mechanical disruption enclosed bacteria presents a promising avenue, aiming induce membrane permeabilization consequent lethal damage. Herein, we introduce hemithioindigo (HTI) motor activated by visible light, capable disrupting...
Abstract Enzymatic peptide synthesis has the potential to be a viable alternative for chemical synthesis. Because of increasing commercial interest in peptides, new and improved enzymatic methods are desirable. In recently developed strategies such as substrate mimetic approaches enzyme‐specific activation, use guanidinophenyl ester (OGp) group been shown suffer from some drawbacks. OGp esters sensitive spontaneous hydrolysis is expensive synthesize therefore not suitable large‐scale...
Abstract The substrate mimetics approach is a versatile method for small‐scale enzymatic peptide‐bond synthesis in aqueous systems. protease‐recognized amino acid side chain incorporated an ester leaving group, the mimetic. This shift of specific moiety enables acceptance acids and peptide sequences that are normally not recognized by enzyme. guanidinophenyl group (OGp), known mimetic serine proteases trypsin chymotrypsin, has now been applied first time combination with papain, cheap...
The modular synthesis and self-assembly behavior of a set peptide-polymer hybrid amphiphiles is described. Gly-Gly-Arg derivatives were conjugated to one the ends hetero-telechelic polystyrene (PS) via either Cu-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction or conventional peptide coupling chemistry. Both conjugation strategies proved be efficient they also applied sequentially create biohybrid ABA-type triblock copolymer, which can considered as macromolecular...
Abstract Methylation of lysine residues in histone proteins is catalyzed by S -adenosylmethionine (SAM)-dependent methyltransferases (KMTs), a genuinely important class epigenetic enzymes biomedical interest. Here we report synthetic, mass spectrometric, NMR spectroscopic and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics studies on KMT-catalyzed methylation peptides that contain its sterically demanding analogs. Our synergistic experimental computational work...
Incomplete resection of prostate cancer may lead to disease recurrence and poor patient outcome. The aim our study was develop bimodal [111In]In-IRDye700DX-prostate specific membrane antigen (PSMA) targeting agents for intra-operative detection photodynamic therapy (PDT) cancer.
Dengue is an important arboviral infectious disease for which there currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (C15H31C(O)-Lys-(Gly Ala)nLys-NHC16H33, shorthand notation C16-KXnK-C16 X = A G, and n 0-2). The representatives 1 2 Ala inhibit dengue protease human furin, two serine proteases involved virus infection that have cationic amino acids as their preferred substrates, IC50...
The development of new antipsychotics with pro-cognitive properties and less side effects represents a priority in schizophrenia drug research. In this study, we present for the first time preclinical exploration promising natural atypical antipsychotic Methyl-2-Amino-3- Methoxybenzoate (MAM), brain-penetrable protoalkaloid from seed plant Nigella damascena. Using animal models related to hyperdopaminergic activity, namely pharmacogenetic apomorphine (D2/D1 receptor agonist)-susceptible...
Abstract Purpose: Strain-promoted azide-alkyne cycloaddition (SPAAC) is a straightforward and multipurpose conjugation strategy. Use of SPAAC to link different functional elements prostate specific membrane antigen (PSMA) ligands would facilitate the development modular platform for PSMA-targeted imaging therapy cancer (PCa). As first proof-of-concept chemistry we synthesized characterized four dual-labeled PSMA intraoperative radiodetection fluorescence PCa. Methods: Ligands were using...