title: Toward a stable α-cycloalkyl amino acid with a photoswitchable cationic side chain.
abstract: The N-alkylated indanylidenepyrroline (NAIP) Schiff base 3 is an unnatural α-amino acid precursor potentially useful for the preparation of semisynthetic peptides and proteins incorporating charged side chains whose structure can be modulated via Z/E photoisomerization. Here we report that the heteroallylic protons of 3 led to partial loss of ethanol accompanied by formation of the novel heterocyclic system 4 during attempted deprotection. We also show that the same protons catalyze the thermal isomerization of 3, making the light-driven conformational control concept ineffective for times longer than a few hours. These problems are not present in the previously unreported compound 5 where the acidic methyl group is replaced by an H atom. Therefore, 5, rather than 3, constitutes a promising prototype for the design of building blocks capable to modulate the electrostatic potential of a protein in specific locations via light irradiation.
authors.affiliation: Dipartimento di Chimica, Università di Siena, via Aldo Moro 2, I-53100 Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rossi Paccani
authors.forename: Donato
authors.initials: D
authors.lastname: Donati
authors.forename: Stefania
authors.initials: S
authors.lastname: Fusi
authors.forename: Loredana
authors.initials: L
authors.lastname: Latterini
authors.forename: Grazia
authors.initials: G
authors.lastname: Farina
authors.forename: Vinicio
authors.initials: V
authors.lastname: Zanirato
authors.forename: Massimo
authors.initials: M
authors.lastname: Olivucci
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D015195:Drug Design; D006860:Hydrogen Bonding; D007536:Isomerism; D007700:Kinetics; D008027:Light; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*; D055668:Photochemical Processes; D011522:Protons; D012545:Schiff Bases / Q000737:chemistry*; D013053:Spectrophotometry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D010455:Peptides; D011522:Protons; D012545:Schiff Bases