title: Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides.
abstract: The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues.
authors.affiliation: Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute , Tampa, Florida 33612, United States.
authors.forename: Chang Won
authors.initials: CW
authors.lastname: Kang
authors.forename: Sujeewa
authors.initials: S
authors.lastname: Ranatunga
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Sarnowski
authors.forename: Juan R
authors.initials: JR
authors.lastname: Del Valle
mesh_terms: D003500:Cyclization; D005449:Fluorenes / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D057786:Peptidomimetics; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: D005449:Fluorenes; D010455:Peptides; D057786:Peptidomimetics; D011724:Pyridazines