title: Incorporation of cis- and trans-4,5-difluoromethanoprolines into polypeptides.
abstract: Substituted prolines exert diverse effects on the backbone conformation of proteins. Novel difluoro-analogues were obtained by adding difluorocarbene to N-Boc-4,5-dehydroproline methyl ester, which gave the trans-adduct as the sole product with 71% yield. Upon cleavage of the N-protection group the free amino acid decomposed rapidly. Its incorporation into the proline-rich cell-penetrating "sweet arrow peptide" was thus accomplished using a dipeptide strategy. Two building blocks, containing either cis- or trans-4,5-difluoromethanoproline, were obtained by difluorocyclopropanation of the aminoacyl derivatives of 4,5-dehydroproline. The resulting dipeptides were stable under standard conditions of Fmoc solid phase peptide synthesis and, thus, suitable to study conformational effects.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry and CFN, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kubyshkin
authors.forename: Pavel K
authors.initials: PK
authors.lastname: Mykhailiuk
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Igor V
authors.initials: IV
authors.lastname: Komarov
mesh_terms: D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis*; D011392:Proline / Q000737:chemistry; D017434:Protein Structure, Tertiary; D060327:Solid-Phase Synthesis Techniques
chemical_list: D006845:Hydrocarbons, Fluorinated; D010455:Peptides; C029999:fluoromethane; D011392:Proline