144876-66-4Relevant academic research and scientific papers
En route towards the peptide γ-helix: X-ray diffraction analyses and conformational energy calculations of Adm-rich short peptides
Mazzier, Daniela,Grassi, Luigi,Moretto, Alessandro,Alemán, Carlos,Formaggio, Fernando,Toniolo, Claudio,Crisma, Marco
, p. 346 - 362 (2017)
We performed the solution-phase synthesis of a set of model peptides, including homo-oligomers, based on the 2-aminoadamantane-2-carboxylic acid (Adm) residue, an extremely bulky, highly lipophilic, tricyclic, achiral, Cα-tetrasubstituted α-amino acid. In particular, for the difficult peptide coupling reaction between two Adm residues, we took advantage of the Meldal's α-azidoacyl chloride approach. Most of the synthesized Adm peptides were characterized by single-crystal X-ray diffraction analyses. The results indicate a significant propensity for the Adm residue to adopt γ-turn and γ-turn-like conformations. Interestingly, we found that a -CO-(Adm)2-NH- sequence is folded in the crystal state into a regular, incipient γ-helix, at variance with the behavior of all of the homo-dipeptides from Cα-tetrasubstituted α-amino acids already investigated, which tend to adopt either the β-turn or the fully extended conformation. Our density functional theory conformational energy calculations on the terminally blocked homo-peptides (n?=?2–8) fully confirmed the crystal-state data, strongly supporting the view that this rigid Cα-tetrasubstituted α-amino acid residue is largely the most effective building block for γ-helix induction, although to a limited length (anti-cooperative effect). Copyright
Synthesis and biological studies of novel neurotensin(8-13) mimetics
Hong, Feng,Zaidi, Javid,Cusack, Bernadette,Richelson, Elliott
, p. 3849 - 3858 (2007/10/03)
Novel neurotensin (NT) (8-13) (Arg8-Arg9-Pro10-Tyr11-Ile 12-Leu13) mimetics 3, 4 were designed by adopting all intrinsic functional groups of the native neurotensin(8-13) and using a substituted indole as a template to mimic the pharmacophore of NT(8-13). Biological studies at subtype 1 of the NT receptor showed that 3 has a 55 and 580 nM binding affinity at rat and human neurotensin receptors, respectively. As a comparison, compounds 5 and 6 were also synthesized. The binding difference between 3, 4 and 5, 6 argues the importance of the carboxylic group in achieving higher potency NT(8-13) mimetics.
Substituted 1-phenyl-3-pyrazolecarboxamides active on neurotensin receptors, their preparation and pharmaceutical compositions containing them
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, (2008/06/13)
The invention relates to new substituted 1-phenyl-3-pyrazolecarboxamides having a great affinity for human neurotensin receptors, to a process for preparing them and to pharmaceutical compositions containing them as active principles. More particularly, this invention relates to the discovery that the affinity for neurotensin receptors, especially human neurotensin receptors, is increased by substituting the phenyl group of 1-phenyl-3-pyrazolecarboxamide compounds with particular groups.
Synthesis and CCK-B Binding Affinities of Cyclic Analogues of the Potent and Selective CCK-B Receptor Antagonist CI-988
Didier, Eric,Horwell, David C.,Pritchard, Martyn C.
, p. 8471 - 8490 (2007/10/02)
A selected series of 14-membered macrocyclic compounds (2) has been prepared as potential CCK-B receptor selective ligands.The efficiency of a number of cyclising reagents has also been evaluated.
