title: Conformational profile of a proline-arginine hybrid.
abstract: The intrinsic conformational preferences of a new nonproteinogenic amino acid have been explored by computational methods. This tailored molecule, named ((β)Pro)Arg, is conceived as a replacement for arginine in bioactive peptides when the stabilization of folded turn-like conformations is required. The new residue features a proline skeleton that bears the guanidilated side chain of arginine at the C(β) position of the five-membered pyrrolidine ring, in either a cis or a trans orientation with respect to the carboxylic acid. The conformational profiles of the N-acetyl-N'-methylamide derivatives of the cis and trans isomers of ((β)Pro)Arg have been examined in the gas phase and in solution by B3LYP/6-31+G(d,p) calculations and molecular dynamics simulations. The main conformational features of both isomers represent a balance between geometric restrictions imposed by the five-membered pyrrolidine ring and the ability of the guanidilated side chain to interact with the backbone through hydrogen bonds. Thus, both cis- and trans-((β)Pro)Arg exhibit a preference for the α(L) conformation as a consequence of the interactions established between the guanidinium moiety and the main-chain amide groups.
authors.affiliation: Departament d'Enginyeria Química, ETS d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, Barcelona E-08028, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Revilla-López
authors.forename: Ana I
authors.initials: AI
authors.lastname: Jiménez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemán
authors.forename: David
authors.initials: D
authors.lastname: Zanuy
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D001120:Arginine; D011392:Proline