1023326-71-7Relevant articles and documents
β2-Homo-amino acid scan of μ-selective opioid tetrapeptide TAPP
Kosson, Piotr,Lipiński, Piotr F. J.,Misicka, Aleksandra,Tymecka, Dagmara
, (2020)
TAPP (H-Tyr-d-Ala-Phe-Phe-NH2) is a potent, μ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β2-Homo-amino acid (β2hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for μ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β2-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β2hPhe4 turned out to bind μOR with affinities equal to that of the parent. β2hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β2-Homologation in the second position gave derivatives with very poor μOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high μOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound.
Synthesis of chiral β2-amino acids by asymmetric hydrogenation
Luehr, Susan,Holz, Jens,Zayas, Odalys,Wendisch, Volkmar,Boerner, Armin
, p. 1301 - 1319 (2012/11/07)
The synthesis of chiral β2-amino acids by homogeneous asymmetric hydrogenation is discussed. Prochiral β-aryl- or β-hetaryl-α-N-benzyl/N-acetyl/N-Boc substituted α- aminomethylacrylates used as substrates were prepared by a Baylis-Hillman react
