160885-93-8Relevant academic research and scientific papers
Synthesis and biological activity of nociceptin/orphanin FQ analogues substituted in position 7 or 11 with Cα,α-dialkylated amino acids
Arduin, Marika,Spagnolo, Barbara,Calo, Girolamo,Guerrini, Remo,Carra, Giacomo,Fischetti, Carmela,Trapella, Claudio,Marzola, Erika,McDonald, John,Lambert, David G.,Regoli, Domenico,Salvadori, Severo
, p. 4434 - 4443 (2007)
Previous structure-activity and NMR studies on nociceptin/orphanin FQ (N/OFQ) demonstrated that Aib substitution of Ala7 and/or Ala11 increases the peptide potency through an alpha helix structure induction mechanism. On these bases we synthesised and evaluated pharmacologically in the mouse vas deferens assay a series of N/OFQ-NH2 analogues substituted in position 7 and 11 with Cα,α-disubstituted cyclic, linear and branched amino acids. None of the 20 novel N/OFQ analogues produced better results than [Aib7]N/OFQ-NH2. Thus, this substitution was combined with other chemical modifications known to modulate peptide potency and/or efficacy generating compound 21 [Nphe1Aib7Arg14Lys15]N/OFQ-NH2 (coded as UFP-111), compound 22 [(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-112) and compound 23 [Phe1Ψ(CH2-NH)Gly2(pF)Phe4Aib7Arg14Lys15]N/OFQ-NH2 (UFP-113). These novel peptides behaved as highly potent NOP receptor ligands showing full (UFP-112) and partial (UFP-113) agonist and pure antagonist (UFP-111) activities in a series of in vitro functional assays performed on pharmacological preparations expressing native as well as recombinant NOP receptors.
An automatic solid-phase synthesis of peptaibols
Hjorringgaard, Claudia U.,Pedersen, Jan M.,Vosegaard, Thomas,Nielsen, Niels Chr,Skrydstrup, Troels
supporting information; experimental part, p. 1329 - 1332 (2009/08/08)
An automated approach to peptaibols using microwave-assisted solid-phase peptide synthesis is demonstrated with a combination of HBTU and acid fluoride mediated couplings for normal and α,α-dialkylated amino acids, respectively. The method is utilized for
Stepwise Automated Solid Phase Synthesis of Naturally Occurring Peptaibols Using FMOC Amino Acid Fluorides
Wenschuh, Holger,Beyermann, Michael,Haber, Hanka,Seydel, Joachim K.,Krause, Eberhard,et al.
, p. 405 - 410 (2007/10/02)
The standard methods of stepwise solid phase synthesis according to Merrifield could not previously be applied to the synthesis of the important naturally occurring peptaibols because of difficulties arising from the pronounced steric hindrance caused by α,α-dialkylated amino acids (incomplete coupling, especially to adjacent similarly constituted units, racemization due to slow coupling to hindered amino acids, etc.), chain degradation due to the presence of acid-labile Aib-Pro linkages, and the lack of any general method for the loading of C-terminal amino alcohols to resin supports.Following recent work on model systems, it is now shown that the adoption of Fmoc amino acid fluorides as coupling reagents makes possible the facile, general assembly of such peptides.The method was demonstrated for alamethicin F30 and F50, saturnisporin SA III, and trichotoxin A50J.The crude products were of remarkable purity.Amino acid analysis, mass spectral data, and comparison of the synthetic alamethicins with samples of naturally occurring material confirmed the success of the syntheses.No significant amount of racemization (0.8percent) was found for any of the chiral amino acids present.The first step of the synthesis involved a new general method for assembly of C-terminal peptide alcohols via the use of o-chlorotrityl resin.In addition, model studies on the question of racemization during the coupling of Fmoc amino acid fluorides are reported.
