title: Hairpin formation promoted by the heterochiral dinipecotic acid segment: A DFT study.
abstract: Conformational preferences for the turn and β-hairpin structures of Ala-based peptides [Ac-Ala(n)-(R)-Nip-(S)-Nip-Ala(n)-X (n = 0-2; X = NHMe or NMe2)] containing nipecotic acid (Nip) residues were carried out using the density functional M06-2X and the implicit solvation model SMD in CH2Cl2 and/or water. The turn structure of the (R)-Nip-(S)-Nip segment with a C10 H-bond between two terminal groups was found to be most preferred (populated at 98.9%) in CH2Cl2; this structure is consistent with IR and (1)H NMR results. The stabilities of the β-hairpins containing the (R)-Nip-(S)-Nip segment as a turn motif relative to the extended structures increased with peptide sequence length. The relative strengths of the H-bonds between the carbonyl oxygen and the amide hydrogen appeared to be responsible for stabilizing the turn and β-hairpin structures in CH2Cl2. In addition, the (R)-Nip-(S)-Nip segment exhibited the capability to be incorporated into one of the two β-turn motifs of gramicidin S (GS). The structure of this GS derivative (GS-Nip2 ) was generally similar to the native peptide but was less hydrophobic and it is therefore expected to exhibit lower hemolytic activity; however, further experiments are needed to evaluate its antimicrobial activity. The structure of GS-Nip2 was somewhat more flexible than GS in solvents of higher polarity. Thus, our calculated results regarding the turn and β-hairpin motifs of the (R)-Nip-(S)-Nip segment indicate that this structure might be useful for the design of bioactive macrocyclic peptides containing β-hairpin mimics as well as binding epitopes in protein-protein and protein-nucleic acid recognitions.
authors.affiliation: Department of Chemistry and BK21 PLUS Research Team, Chungbuk National University, Cheongju, Chungbuk, 362-763, Republic of Korea.
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Kang
authors.affiliation: Department of Nursing, Cheju Halla University, Cheju, 690-708, Republic of Korea.
authors.forename: Hae Sook
authors.initials: HS
authors.lastname: Park
mesh_terms: D006860:Hydrogen Bonding; D009557:Nipecotic Acids / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D009557:Nipecotic Acids; D010455:Peptides; D011506:Proteins; D012997:Solvents; C030278:nipecotic acid
keywords: density functional calculations; hairpin structures; nipecotic acid residue; solvent effects; turn structure