A5013086615- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Pain Mechanisms and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Biochemical and Structural Characterization
- Influenza Virus Research Studies
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Sphingolipid Metabolism and Signaling
- Medicinal Plants and Bioactive Compounds
- Pharmacological Effects and Assays
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Treatment and Pharmacology
- Dyeing and Modifying Textile Fibers
- Silk-based biomaterials and applications
- Wound Healing and Treatments
- Paraoxonase enzyme and polymorphisms
- Gastrointestinal motility and disorders
- Barrier Structure and Function Studies
- Immune Response and Inflammation
- Diet and metabolism studies
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Immunotherapy and Immune Responses
Polish Academy of Sciences
2014-2024
Mossakowski Medical Research Institute, Polish Academy of Sciences
2014-2024
In-Q-Tel
2019
Vrije Universiteit Brussel
2005-2008
Interactions of 21 fentanyl derivatives with μ-opioid receptor (μOR) were studied using experimental and theoretical methods. Their binding to μOR was assessed radioligand competitive assay. A uniform set affinity data contains values for two novel one previously uncharacterized derivative. The confirms trends known so far thanks their uniformity, they facilitate further comparisons. In order provide structural hypotheses explaining the affinities, complexes modeled subject molecular...
Herein, the opioid pharmacophore H-Dmt-d-Arg-Aba-β-Ala-NH2 (7) was linked to peptide ligands for nociceptin receptor. Combination of 7 and NOP (e.g., H-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) led binding affinities in low nanomolar domain. In vitro, hybrids behaved as agonists at receptors antagonists Intravenous administration hybrid 13a (H-Dmt-d-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2) mice resulted potent long lasting antinociception tail-flick test, indicating that able permeate BBB. This further...
Highly pathogenic avian influenza viruses are a serious threat to domestic poultry and can be source of new human pandemic annual strains. Vaccination is the main strategy protection against influenza, thus generation vaccines, including DNA needed. One promising approach for enhancing immunogenicity vaccine maximize its expression in immunized host. The three variants encoding hemagglutinin (HA) from virus A/swan/Poland/305-135V08/2006 (H5N1) was compared two animal models, mice (BALB/c)...
Abstract Keratin is an interesting protein needed for wound healing and tissue recovery. We have recently proposed a new, simple inexpensive method to obtain fur hair keratin‐derived biomaterials suitable medical application. The aim of the study was evaluate role (FKDP) dressing in allogenic full‐thickness surgical skin model. data obtained using scanning electron microscopy showed that employed processed biomaterial had higher surface porosity compared with control raw material. From MTS...
Background: The clinical treatment of various types pain relies upon the use opioid analgesics. However most them produce, in addition to analgesic effect, several side effects such as development dependence and addiction well sedation, dysphoria, constipation. One solution these problems are chimeric compounds which pharmacophore is hybridized with another type compound incease antinociceptive effects. Neurotensin-induced antinociception not mediated through system. Therefore, hybridizing...
The area of multitarget compounds, joining two pharmacophores within one molecule, is a vivid field research in medicinal chemistry. Not only pharmacophoric elements are essential for the design and activity such but type length linkers used to connect them also crucial. In present contribution, we describe compound 1 which typical opioid peptide sequence combined with fragment characteristic neurokinin-1 receptor (NK1R) antagonists through hydrazone bridge. has high affinity μ- δ-opioid...
Biphalin is an opioid peptide analogue that currently under clinical development as a new type of site-directed analgesic. In rats, the intrathecal (i.t.) analgesic potency biphalin 1000-fold greater than morphine. Such high activity may reflect this compound's activation three types receptors (mu, delta and kappa). NMDA also play important role in nociceptive processing. Therefore, we investigated rats whether antagonist influence biphalin-induced antinociception. present study, ketamine...
Abstract Background An important limiting factor in the development of centrally acting pharmaceuticals is blood-brain barrier (BBB). Transport therapeutic peptides through this highly protective physiological remains a challenge for peptide drug delivery into central nervous system (CNS). Because most common strategy to treat moderate severe pain consists activation opioid receptors brain, active analogues as potential analgesics requires compounds with high resistance enzymatic degradation...
The design and synthesis of leu-enkephalin analogs by replacing the glycine residues with N -(2-thioethyl)glycines opening cyclisation potential is presented.
Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where d-Ala(2) and Gly(4) N-methylated, Phe(3)-Gly(4) residue substituted the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities nanomolar range for both μ- δ-opioid receptors but no detectable affinity κ-opioid receptor. Measurements cAMP accumulation, phosphorylation extracellular signal-regulated kinase (ERK1/2) HEK293 cells stably expressing each...
The synthesis of conformationally restricted dipeptidic moieties 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba)-Gly ([(4S)-amino-3-oxo-1,2,4,5-tetrahydro-1H-2-benzazepin-2-yl]-acetic acid) and 8-hydroxy-4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Hba)-D-Ala ([(4S)-amino-8-hydroxy-3-oxo-1,2,4,5-tetrahydro-benzo[c]azepin-2-yl]-propionic was based on a synthetic strategy that uses an oxazolidinone as N-acyliminium precursor. Introducing these Aba scaffolds into the N-terminal...
Two dermorphin analogues having an almost identical structure but different structural flexibility were compared for opioid activity. In 1 the aromatic side chains incorporated into a lactam structure, while in 2 N-amide alkylation was retained flexible. Both compounds produced comparable antinociceptive effects mouse tail flick test after peripheral administration. This indicates that lipophilicity, rather than chain flexibility, is key determinant blood−CNS barrier penetration.
Herein, the synthesis and biological evaluation of dual opioid agonists–neurokinin 1 receptor (NK1R) antagonists is described. In these multitarget ligands, two pharmacophores do not overlap, this allowed maintaining high NK1R affinity antagonist potency in compounds 12 13. Although fusion ligands resulted slightly diminished agonism at μ- δ-opioid receptors (MOR DOR, respectively), as compared to parent peptide, balanced MOR/DOR activities were obtained. Compared morphine, 13 produced more...
On the basis of structural features Dmt-Tic pharmacophore, a new motif leading to fairly potent μ-opioid antagonist is described. This contains 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-one skeleton as substitute for Tic residue, which provides conformational constraint compatible with receptor. The stereoselective synthesis four stereoisomers performed starting from homochiral 2‘,6‘-dimethyltyrosine (Dmt) and o-aminomethylphenylalanine.
Hemagglutinin glycoprotein (HA) is a principle influenza vaccine antigen. Recombinant HA-based vaccines become potential alternative for traditional approach. Complexity and variation of HA N-glycosylation are considered as the important factors design. The number location glycan moieties in molecule also crucial. Therefore, we decided to study effect pattern on H5 antigen structure its ability induce immunological response. We change neither nor position glycosylation sites but only length....
beta-Amino acids containing hybrid peptides and beta-peptides show great potential as peptidomimetics. In this paper we describe the synthesis affinity toward micro- delta-opioid receptors of beta-peptides, analogues Leu-enkephalin, deltorphin I, dermorphin alpha,beta-hybrides, I. Substitution alpha-amino acid residues with beta(3)-homo-amino residues, in general resulted decrease to opioid receptors. However, incorporation beta(3)h-D-Ala position 2 or beta(3)hPhe 3 I potent selective ligand...
In the present contribution, we analyze influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered were based either