title: Racemic synthesis and solid phase peptide synthesis application of the chimeric valine/leucine derivative 2-amino-3,3,4-trimethyl-pentanoic acid.
abstract: The synthesis of non natural amino acid 2-amino-3,3,4-trimethyl-pentanoic acid (Ipv) ready for solid phase peptide synthesis has been developed. Copper (I) chloride Michael addition, followed by a Curtius rearrangement are the key steps for the lpv synthesis. The racemic valine/leucine chimeric amino acid was then successfully inserted in position 5 of neuropeptide S (NPS) and the diastereomeric mixture separated by reverse phase HPLC. The two diastereomeric NPS derivatives were tested for intracellular calcium mobilization using HEK293 cells stably expressing the mouse NPS receptor where they behaved as partial agonist and pure antagonist.
authors: M
authors: M
authors: Pelà
authors: L
authors: L
authors: Del Zoppo
authors: L
authors: L
authors: Allegri
authors: E
authors: E
authors: Marzola
authors: C
authors: C
authors: Ruzza
authors: G
authors: G
authors: Calo
authors: E
authors: E
authors: Perissutti
authors: F
authors: F
authors: Frecentese
authors: S
authors: S
authors: Salvadori
authors: R
authors: R
authors: Guerrini
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003300:Copper; D057809:HEK293 Cells; D006801:Humans; D007202:Indicators and Reagents; D007930:Leucine / Q000737:chemistry*; D051379:Mice; D010421:Pentanoic Acids / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis*; D060327:Solid-Phase Synthesis Techniques; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014633:Valine / Q000737:chemistry*
chemical_list: C000591033:2-amino-3,3,4-trimethyl-pentanoic acid; D007202:Indicators and Reagents; D010421:Pentanoic Acids; D010455:Peptides; D003300:Copper; C028419:cuprous chloride; D007930:Leucine; D014633:Valine; D002118:Calcium