An Improved Method for Synthesis of <scp>l</scp>-Homoglutamic Acid <i>via</i> Epsilon-<i>N</i>-deamination of <scp>l</scp>-Lysine Derivative

Kondo, Michio; Miyazaki, Kouji; Kodama, Hiroaki; Horimoto, Hideaki

doi:10.1246/bcsj.58.1171

Cited by 6 publications

(2 citation statements)

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“…The terminal amino group of LeuOEt was acetylated following a published procedure. 25 The deuteriated solvents were obtained from either Aldrich Chemical Co. or Cambridge Isotope Laboratories, Inc. All other chemicals were obtained from Aldrich Chemical Co. The peptides were synthesized by a standard solid-state method, and their purity was checked by HPLC separation and MALDI mass spectroscopy.…”

Section: Methodsmentioning

confidence: 99%

“…Distilled water was demineralized to a resistivity greater than 16 MΩ·cm by a Barnsted Nanopure II apparatus and purified further with Chelex 100 resin from Bio-Rad Co. Amino acid esters AcLysOMe, AcTyrOEt, AcPheOEt, and LeuOEt and the salt CD 3 COONa were obtained from Sigma Chemical Co. The terminal amino group of LeuOEt was acetylated following a published procedure …”

Section: Methodsmentioning

confidence: 99%

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The Role of Cation−π Interactions in Biomolecular Association. Design of Peptides Favoring Interactions between Cationic and Aromatic Amino Acid Side Chains

et al. 2001

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Cation-pi interactions between amino acid side chains are increasingly being recognized as important structural and functional features of proteins and other biomolecules. Although these interactions have been found in static protein structures, they have not yet been detected in dynamic biomolecular systems. We determined, by (1)H NMR spectroscopic titrations, the energies of cation-pi interactions of the amino acid derivative AcLysOMe (1) with AcPheOEt (2) and with AcTyrOEt (3) in aqueous and three organic solvents. The interaction energy is substantial; it ranges from -2.1 to -3.4 kcal/mol and depends only slightly on the dielectric constant of the solvent. To assess the effects of auxiliary interactions and structural preorganization on formation of cation-pi interactions, we studied these interactions in the association of pentapeptides. Upon binding of the positively-charged peptide AcLysLysLysLysLysNH(2) (5) to the negatively-charged partner AcAspAspXAspAspNH(2) (6), in which X is Leu (6a), Tyr (6b), and Phe (6c), multiple interactions occur. Association of the two pentapeptides is dynamic. Free peptides and their complex are in fast exchange on the NMR time-scale, and 2D (1)H ROESY spectra of the complex of the two pentapeptides do not show intermolecular ROESY peaks. Perturbations of the chemical shifts indicated that the aromatic groups in peptides 6b and 6c were affected by the association with 5. The association constants K(A) for 5 with 6a and with 6b are nearly equal, (4.0 +/- 0.7) x 10(3) and (5.0 +/- 1.0) x 10(3) M(-)(1), respectively, while K(A) for 5 with 6c is larger, (8.3 +/- 1.3) x 10(3) M(-)(1). Molecular-dynamics (MD) simulations of the pentapeptide pairs confirmed that their association is dynamic and showed that cation-pi contacts between the two peptides are stereochemically possible. A transient complex between 5 and 6 with a prominent cation-pi interaction, obtained from MD simulations, was used as a template to design cyclic peptides C(X) featuring persistent cation-pi interactions. The cyclic peptide C(X) had a sequence in which X is Tyr, Phe, and Leu. The first two peptides do, but the third does not, contain the aromatic residue capable of interacting with a cationic Lys residue. This covalent construct offered conformational stability over the noncovalent complexes and allowed thorough studies by 2D NMR spectroscopy. Multiple conformations of the cyclic peptides C(Tyr) and C(Phe) are in slow exchange on the NMR time-scale. In one of these conformations, cation-pi interaction between Lys3 and Tyr9/Phe9 is clearly evident. Multiple NOEs between the side chains of residues 3 and 9 are observed; chemical-shift changes are consistent with the placement of the side chain of Lys3 over the aromatic ring. In contrast, the cyclic peptide C(Leu) showed no evidence for close approach of the side chains of Lys3 and Leu9. The cation-pi interaction persists in both DMSO and aqueous solvents. When the disulfide bond in the cyclic peptide C(Phe) was removed, the cation-pi interaction in the acycli...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%