Publicaties
Gekozen filters:
Gekozen filters:
Synthesis, Biological Evaluation, and Automated Docking of Constrained Analogues of the Opioid Peptide H-Dmt-D-Ala-Phe-Gly-NH2 Using the 4- or 5-Methyl Substituted 4-Amino-1,2,4,5-tetrahydro-2-benzazepin-3-one Scaffold Vrije Universiteit Brussel
Abstract: The Phe(3) residue of the N-terminal tetrapeptide of dermorphin (H-Dmt-D-Ala-Phe-Gly-NH2) was conformationally constrained using 4- or 5-methyl-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) stereoisomeric scaffolds. Several of the synthesized peptides were determined to be high affinity agonists for the mu opioid receptor (OPRM) with selectivity over the delta opioid receptor (OPRD). Interesting effects of the Aba ...
Side Chain Cyclized Aromatic Amino Acids: Great Tools as Local Constraints in Peptide and Peptidomimetic Design. IF 6.259 Vrije Universiteit Brussel
Convergence and constraint in the cranial evolution of mosasaurid reptiles and early cetaceans Universiteit Antwerpen
The repeated return of tetrapods to aquatic life provides some of the best-known examples of convergent evolution. One comparison that has received relatively little focus is that of mosasaurids (a group of Late Cretaceous squamates) and archaic cetaceans (the ancestors of modern whales and dolphins), both of which show high levels of craniodental disparity, similar initial trends in locomotory evolution, and global distributions. Here we ...
Efficient One-Pot Access to Trisubstituted 2-Benzazepin-3-ones as Constrained Pseudopeptide Analogues and Privileged Scaffolds. IF 2.53 Vrije Universiteit Brussel
Background: Benzazepines received great attention in the field of medicinal chemistry since this scaffold has been recognized to belong to the important family of privileged templates. More specifically, the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) is used as a core structure in a variety of constrained therapeutic peptide (turn) mimetics. Most of the synthetic approaches towards this template have focused on cyclizations which ...
Locally constrained, azepinone-containing human MC4R agonist and human MC5R antagonist tetrapeptide ligands Universiteit Gent
Design of Novel Neurokinin 1 Receptor Antagonists Based on Conformationally Constrained Aromatic Amino Acids and Discovery of a Potent Chimeric Opioid Agonist-Neurokinin 1 Receptor Antagonist Vrije Universiteit Brussel
Abstract: A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3',5'-(CF3)(2)-Bn] 20 [Ac-Aba-Gly-NMe-3',5'-(CF3)(2)-Bn], and 23 [Ac-Tic-NMe-3',5'-(CF3)(2)-Bn], which were able to counteract the agonist effect of substance P, the endogenous ligand of NK1R. The most active NK1 antagonist ...
Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist – Neurokinin-1 antagonist peptidomimetics. 3.902 Vrije Universiteit Brussel
Abstract
A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3?,5?-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-?-Ala-NMe-Bn) were selected for in vivo behavioural assays, which were conducted in acute (tail-flick) and ...
A reported mixed opioid agonist - neurokinin 1 receptor (NK1R) antagonist 4 (Dmt-D-Arg-Aba-Gly-(3?,5?-(CF3)2)NMe-benzyl) was modified to identify important features in both pharmacophores. The new dual ligands were tested in vitro and subsequently two compounds (lead structure 4 and one of the new analogues 22, Dmt-D-Arg-Aba-?-Ala-NMe-Bn) were selected for in vivo behavioural assays, which were conducted in acute (tail-flick) and ...
Propargylamine Amino Acids as Constrained Ne-Substituted Lysine Mimetics Vrije Universiteit Brussel
Herein, alkylated propargylamines are reported as constrained lysine mimetics and constructed in a single step using a copper(I)-catalyzed A3-coupling reaction. Using multiple secondary amines, the reaction allowed the generation of a structurally diverse set of N-Fmoc protected amino acid derivatives. In addition, the A3-reaction was applied on solid phase via the assembly of short model tripeptides. Moreover, the internal alkyne moiety allowed ...
Amino Triazolo Diazepines (Ata) as Constrained Histidine Mimics Vrije Universiteit Brussel
Abstract: Two synthetic routes for the synthesis of amino-triazolodiazepine (Ata) scaffolds are presented. The scope of both of these proceeding through key intra- and intermolecular Huisgen cycloaddition reactions is discussed. The replacement of the His-Pro dipeptide segment in angiotensin IV by the dipeptide mimetic Ata-Gly and subsequent biological evaluation in two inhibitory enzyme assays validated the use of the Ata moiety as a His mimic ...