Conformational profile of a proline-arginine hybrid.
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.
Revilla-López
Guillermo
G
Departament d'Enginyeria Química, ETS d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, Barcelona E-08028, Spain.
Jiménez
Ana I
AI
Cativiela
Carlos
C
Nussinov
Ruth
R
Alemán
Carlos
C
Zanuy
David
D
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
D009842:Oligopeptides; D001120:Arginine; D011392:Proline