477775-35-2Relevant academic research and scientific papers
Single Peptide Backbone Surrogate Mutations to Regulate Angiotensin GPCR Subtype Selectivity
Vrettos, Eirinaios I.,Valverde, Ibai E.,Mascarin, Alba,Pallier, Patrick N.,Cerofolini, Linda,Fragai, Marco,Parigi, Giacomo,Hirmiz, Baydaa,Bekas, Nick,Grob, Nathalie M.,Stylos, Evgenios Κ.,Shaye, Hamidreza,Del Borgo, Mark,Aguilar, Marie-Isabel,Magnani, Francesca,Syed, Nelofer,Crook, Timothy,Waqif, Emal,Ghazaly, Essam,Cherezov, Vadim,Widdop, Robert E.,Luchinat, Claudio,Michael-Titus, Adina T.,Mindt, Thomas L.,Tzakos, Andreas G.
, p. 10690 - 10694 (2020/07/25)
Mutating the side-chains of amino acids in a peptide ligand, with unnatural amino acids, aiming to mitigate its short half-life is an established approach. However, it is hypothesized that mutating specific backbone peptide bonds with bioisosters can be exploited not only to enhance the proteolytic stability of parent peptides, but also to tune its receptor subtype selectivity. Towards this end, four [Y]6-Angiotensin II analogues are synthesized where amide bonds have been replaced by 1,4-disubstituted 1,2,3-triazole isosteres in four different backbone locations. All the analogues possessed enhanced stability in human plasma in comparison with the parent peptide, whereas only two of them achieved enhanced AT2R/AT1R subtype selectivity. This diversification has been studied through 2D NMR spectroscopy and unveiled a putative more structured microenvironment for the two selective ligands accompanied with increased number of NOE cross-peaks. The most potent analogue, compound 2, has been explored regarding its neurotrophic potential and resulted in an enhanced neurite growth with respect to the established agent C21.
Synthesis of 11C-labeled Sulfonyl Carbamates through a Multicomponent Reaction Employing Sulfonyl Azides, Alcohols, and [11C]CO
Stevens, Marc Y.,Chow, Shiao Y.,Estrada, Sergio,Eriksson, Jonas,Asplund, Veronika,Orlova, Anna,Mitran, Bogdan,Antoni, Gunnar,Larhed, Mats,?berg, Ola,Odell, Luke R.
, p. 566 - 573 (2016/12/22)
We describe the development of a new methodology focusing on 11C-labeling of sulfonyl carbamates in a multicomponent reaction comprised of a sulfonyl azide, an alkyl alcohol, and [11C]CO. A number of 11C-labeled sulfonyl carbamates were synthesized and isolated, and the developed methodology was then applied in the preparation of a biologically active molecule. The target compound was obtained in 24±10 % isolated radiochemical yield and was evaluated for binding properties in a tumor cell assay; in vivo biodistribution and imaging studies were also performed. This represents the first successful radiolabeling of a non-peptide angiotensin II receptor subtype 2 agonist, C21, currently in clinical trials for the treatment of idiopathic pulmonary fibrosis.
Design, synthesis, and biological evaluation, of the first selective nonpeptide AT2 receptor agonist
Wan, Yiqian,Wallinder, Charlotta,Plouffe, Bianca,Beaudry, Hélène,Mahalingam,Wu, Xiongyu,Johansson, Berndt,Holm, Mathias,Botoros, Milad,Karlén, Anders,Pettersson, Anders,Nyberg, Fred,F?ndriks, Lars,Gallo-Payet, Nicole,Hallberg, Anders,Alterman, Mathias
, p. 5995 - 6008 (2007/10/03)
The first druglike selective angiotensin II AT2 receptor agonist (21) with a Ki value of 0.4 nM for the AT2 receptor and a Ki > 10 μM for the AT1 receptor is reported. Compound 21, with a bioavailability of 20-3
