88556-26-7Relevant academic research and scientific papers
"clickable" Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals
Bachmann, Michael,Brandt, Florian,Kopka, Klaus,Laube, Markus,Pietzsch, Jens,Ullrich, Martin,Wodtke, Robert,L?ser, Reik,Pietzsch, Hans-Jürgen,Van Den Hoff, J?rg
supporting information, p. 710 - 733 (2022/01/11)
The intentional binding of radioligands to albumin gains increasing attention in the context of radiopharmaceutical cancer therapy as it can lead to an enhanced radioactivity uptake into the tumor lesions and, thus, to a potentially improved therapeutic outcome. However, the influence of the radioligand's albumin-binding affinity on the time profile of tumor uptake has been only partly addressed so far. Based on the previously identified N?-4-(4-iodophenyl)butanoyl-lysine scaffold, we designed "clickable"lysine-derived albumin binders (cLABs) and determined their dissociation constants toward albumin by novel assay methods. Structure-activity relationships were derived, and selected cLABs were applied for the modification of the somatostatin receptor subtype 2 ligand (Tyr3)octreotate. These novel conjugates were radiolabeled with copper-64 and subjected to a detailed in vitro and in vivo radiopharmacological characterization. Overall, the results of this study provide an incentive for further investigations of albumin binders for applications in endoradionuclide therapies.
Comparison of the inhibition of human and Trypanosoma cruzi prolyl endopeptidases
Vendeville, Sandrine,Goossens, Filip,Debreu-Fontaine, Marie-Ange,Landry, Valérie,Davioud-Charvet, Elisabeth,Grellier, Philippe,Scharpe, Simon,Sergheraert, Christian
, p. 1719 - 1729 (2007/10/03)
Prolyl endopeptidases (PEPs) have been found in numerous species. Inhibitors of human enzyme could correct cognitive deficits in Alzheimer patients while inhibition of Trypanosoma cruzi PEP could prevent invasion phase in Chagas disease. A structure-activity relationship study carried out in a tetrahydroisoquinoline series allowed to obtain potent competitive inhibitors superior to SUAM-1221. Besides, inhibitors expected to act according to an irreversible mechanism revealed to be superior to JPT-4819, for applications linked to human enzyme inhibition.
Development of Potent and Selective CCK-A Receptor Agonists from Boc-CCK-4: Tetrapeptides Containing Lys(Nε)-Amide Residues
Shiosaki, Kazumi,Lin, Chun Wel,Kopecka, Hana,Craig, Richard A.,Bianchi, Bruce R.,et al.
, p. 2007 - 2014 (2007/10/02)
A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(Nε-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-A receptor agonists.These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al.J.Med.Chem. 1991,34,2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series.A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives.Sulfation of phenolic amides appended onto the ε-amino group of the lysine did not affect affinity for the CCK-A receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor.The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis.Both effects were blocked by selective CCK-A receptor antagonists
