Glycine Dipeptide Research Articles

Structure Determination of Zinc and Cadmium Dication Complexes with Intact and Deprotonated Histidyl Glycine and Glycyl Histidine Dipeptides.

Metalated intact and deprotonated histidyl glycine and glycyl histidine dipeptides were investigated in the gas phase by using infrared multiple photon dissociation (IRMPD) spectroscopy with light from a free-electron laser (FEL). The dipeptides M2+(GlyHis), M2+(HisGly), [M(GlyHis-H)]+, and [M(HisGly-H)]+, where M = Zn and Cd, were probed to elucidate how the His position along the peptide chain and ligand charge state might influence the structures observed in the gas phase. Simulated annealing calculations were performed to determine energetically low-lying conformers and isomers of these structures. Quantum chemical calculations were used to optimize the structures at the B3LYP level of theory using the 6-311+G(d,p) and def2-TZVP basis sets for zinc and cadmium complexes, respectively. IRMPD and calculated linear absorption spectra were compared to evaluate which structures are present. Relative energies of the various species were evaluated using single-point energy calculations for low-lying structures at the B3LYP, B3LYP-GD3BJ, ωB97XD, and MP2(full) levels using the 6-311+G(2d,2p) and def2-TZVPP basis sets. For all species, structures for both metals mirror each other, and those that reproduce the experimental spectrum were determined to be iminol structures for the intact ligands or iminol-like structures for the deprotonated ligands. Additionally, when the spectra of the deprotonated dipeptides are compared to the intact dipeptides, the change in the spectra is correlated to the group that is deprotonated.

Accurate Reproduction of Quantum Mechanical Many-Body Interactions in Peptide Main-Chain Hydrogen-Bonding Oligomers by the Polarizable Gaussian Multipole Model.

A key advantage of polarizable force fields is their ability to model the atomic polarization effects that play key roles in the atomic many-body interactions. In this work, we assessed the accuracy of the recently developed polarizable Gaussian Multipole (pGM) models in reproducing quantum mechanical (QM) interaction energies, many-body interaction energies, as well as the nonadditive and additive contributions to the many-body interactions for peptide main-chain hydrogen-bonding conformers, using glycine dipeptide oligomers as the model systems. Two types of pGM models were considered, including that with (pGM-perm) and without (pGM-ind) permanent atomic dipoles. The performances of the pGM models were compared with several widely used force fields, including two polarizable (Amoeba13 and ff12pol) and three additive (ff19SB, ff15ipq, and ff03) force fields. Encouragingly, the pGM models outperform all other force fields in terms of reproducing QM interaction energies, many-body interaction energies, as well as the nonadditive and additive contributions to the many-body interactions, as measured by the root-mean-square errors (RMSEs) and mean absolute errors (MAEs). Furthermore, we tested the robustness of the pGM models against polarizability parameterization errors by employing alternative polarizabilities that are either scaled or obtained from other force fields. The results show that the pGM models with alternative polarizabilities exhibit improved accuracy in reproducing QM many-body interaction energies as well as the nonadditive and additive contributions compared with other polarizable force fields, suggesting that the pGM models are robust against the errors in polarizability parameterizations. This work shows that the pGM models are capable of accurately modeling polarization effects and have the potential to serve as templates for developing next-generation polarizable force fields for modeling various biological systems.

Dietary Collagen Hydrolysates Retard Estrogen Deficiency-Induced Bone Loss through Blocking Osteoclastic Activation and Enhancing Osteoblastic Matrix Mineralization

Osteoporosis manifest in postmenopausal women is an osteolytic disease characterized by bone loss, leading to increased susceptibility to bone fractures and frailty. The use of complementary therapies to alleviate postmenopausal osteoporosis is fairly widespread among women. The current study examined that Pangasius hypophthalmus fish skin collagen hydrolysates (fsCH) inhibited ovariectomy (OVX)-induced bone loss by conducting inter-comparative experiments for anti-osteoporotic activity among 206–618 mg/kg fsCH, 2 mg/kg isoflavone, 15 mg/kg glycine–proline–hydroxyproline (GPH) tripeptide, and calcium lactate. Surgical estrogen loss of mice for 8 weeks reduced serum 17β-estradiol levels with uterus atrophy, which was ameliorated by orally administering fsCH or isoflavone to mice. Similar to isoflavone, fsCH containing GPH-enhanced bone mineral density reduced levels of cathepsin K and proton-handling proteins, and elevated collagen 1 level in OVX bones. The treatment with fsCH and isoflavone enhanced the serum levels of collagen synthesis-related procollagen type 1 carboxy/amino-terminal propeptides reduced by OVX, whereas serum levels of osteocalcin and alkaline phosphatase, as well as collagen breakdown-related carboxy/amino-terminal telopeptides of type 1 collagen were reduced in OVX mice treated with fsCH, isoflavone, and calcium lactate. The trabecular bones were newly formed in OVX bones treated with isoflavone and fsCH, but not with calcium lactate. However, a low-dose combination of fsCH and calcium lactate had a beneficial synergy effect on postmenopausal osteoporosis. Furthermore, similar to isoflavone, 15–70 μg/mL fsCH, with its constituents of GPH and dipeptides of glycine–proline and proline–hydroxyproline, enhanced osteogenesis through stimulating differentiation, matrix mineralization, and calcium deposition of MC3T3-E1 osteoblasts. Accordingly, the presence of fsCH may encumber estrogen deficiency-induced bone loss through enhancing osteoclastogenic differentiation and matrix collagen synthesis. Therefore, fsCH may be a natural compound retarding postmenopausal osteoporosis and pathological osteoresorptive disorders.

The effect of chain length and side chains on the solubility of peptides in water from 278.15 K to 313.15 K: A case study in glycine homopeptides and dipeptides

The thermodynamic properties of peptides are significant in terms of the crystallization conditions of biomaterials. In this work, we seek to understand and explain the effect of side chains and chain length on the solubility of peptides. The amino acid residues of dipeptides investigated here were chosen based on their difference in side chain properties. The modified Apelblat equation was used to correlate the relationship between the solubility in water and temperature. In order to explore solute–solvent interactions, the solvation free energies of these peptides were calculated by Molecular Dynamic simulations. This work gives an indication of the effects of side chains and chain length on the solubility of amino acids and peptides in water under different temperatures, which not only provides the thermodynamic data for peptides, but is also critical in the prediction of peptide solubility using Statistical Associating Fluid Theory (SAFT).

An MP2/Molecular Dynamics study of the solvent effects on the conformational equilibrium of the glycine dipeptide

The solvent effects on the conformational equilibrium of the Glycine dipeptide are studied using a Quantum Mechanics/Molecular Mechanics method based on the mean field approximation. Glycine is the structurally simplest amino acid found in nature and is usually considered the amino acid that best conforms to the basic assumptions of the random coil model. It has been experimentally found, however, that in gas phase the conformational landscape of the glycine dipeptide is dominated by only two structures (C5 and C7) characterized by the formation of an intramolecular hydrogen bond (HB). In this work we show that a similar situation is found in water solution: the conformational equilibrium is also dominated by only two structures (PPII and α) that, furthermore, are not stable in gas phase and in which the intramolecular HB is replaced by an intermolecular HB. This behavior mimics that of other peptides which display less conformational freedom. We show that relative stability results from the interplay of two free energy components that operate in opposite directions: internal energy and dipeptide-water interaction energy. The influence exerted by the solvent structure and the dipeptide charge distribution on the relative stability of the different conformers is also analyzed.

Interaction of evaporated glycine and dipeptide derivatives of glycine with He2+ ions

In this paper we have studied a mechanism for radiation damage of gas phase molecules of glycine [Gly] and dipeptide derivatives of glycine, such as diglycine [Gly-Gly], cyclo(glycylglycyl) [cyclo(Gly-Gly)] and glycyl-leucine [Gly-Leu] by the impact of He2+ ions with energy Ep = 4 keV/u. Relative cross sections of different elementary processes occurring in single collisions between dipeptide derivatives of glycine and ions have been measured for the first time. The fragmentation channels of both singly and multiply charged molecular ions have been studied experimentally. It has been shown that in the process of Gly-Gly sublimation, cyclization in the crystalline sample takes place, which results in formation of cyclo(Gly-Gly). Using the DFT method, the geometry of molecules and singly charged ions of glycine dipeptide derivatives has been calculated, as well as energies of different experimentally observed fragmentation channels of these ions.

Multi-functionalized Cellulosic Biomass by Plasma-Assisted Bonding of α-Amino Carboxylic Acid to Enhance the Removal of Ibuprofen in Aqueous Solution

The present study concerns the removal of ibuprofen (IBP) from aqueous medium using glycine grafted plasma-modified cocoa shell as an effective and promising sorbent. The plasma pretreatment prior to the grafting process creates hydroxyl (–OH), carbonyl (–CO) and carboxyl (–COOH) groups, which were used as binder sites for glycine graft immobilization. The grafting technique was successful as an IR spectra of grafted biosorbent exhibited specific functional groups (N–H, C–N, –OH, C=O, COOH), which were characteristics of newly formed atomic bonds. The attachment to biomass was made through a single glycine and a glycine dipeptide esterified. The results of the removal tests demonstrated that the amounts of IBP uptake at equilibrium were higher with glycine grafted biomass (BG) than un-grafted, so going from 15.24 to 19.88 mg/g for initial 20 mg/L IBP and from 23.18 to 26.98 mg/g for 30 mg/L IBP. Amongst the tested kinetics model to predict adsorption behavior of the experimental results, the Avrami fractional-order model was the most suitable. The values of ΔH° and ΔG° suggested a spontaneous and exothermic process, which is typical for physical interaction in accordance with the Liu best-fitted isotherm model.

Electrostatic Effects on the Stability of Peptide Radicals.

We explored the influence of external electric fields (EEFs) on the stability of a glycine dipeptide model radical using high-level quantum chemical methods. Remotely located ions (Cl-/Na+) are used to implement EEF effects. The effects of these ions are reproduced using background point charges and oriented EEFs. Remote charges as far as 900 pm from the Cα radical center can be significantly stabilizing or destabilizing as a function of their relative orientation. The magnitude of these effects is also strongly dependent on the distance between the radical center and the charge location. After examining the strengths and weaknesses of some frequently used quantum mechanics methods in describing these effects properly, a comparison is made on the stability of dipeptide radicals bearing protonable or deprotonable side chains. In this group, the stability of the respective Cα radicals mainly depends on the preferred orientation of the charge-carrying side chain.

The opposite effect of K+ and Na+ on the hydrolysis of linear and cyclic dipeptides

Potassium and sodium are generally considered inert ‘spectator’ ions for organic reactions. Here, we report rate constants for the acid-promoted hydrolysis of the seven dipeptides of glycine (G) and alanine (A) and an unexpected pattern in how these rates differ in the presence of K+ and Na+. The linear dipeptides hydrolyze 12–18% percent slower in the presence of KCl versus an equal concentration of NaCl, while the cyclic dipeptides hydrolyze 5–13% faster in the presence of KCl (all P-values < 0.025). We believe this is the first report of a general organic reaction—here, amide hydrolysis—for which some substrates react faster in the presence of K+ and others in Na+. The results offer a potential reason for life’s mysterious universal selection of intracellular potassium over sodium.

Comparative conformational analyses and molecular dynamics studies of glycylglycine methyl ester and glycylglycine N-methylamide

Amide–ester substitution and water models significantly alter conformational and solvation properties of glycine–glycine dipeptides.

Leucine and glycine dipeptides of porcine placenta ameliorate physical fatigue through enhancing dopaminergic systems.

Fatigue is a common and serious health problem, and various dietary interventions have previously been employed to ameliorate fatigue. The aim of the current study was to investigate the anti‑fatigue effects of Danish porcine placenta (DPP) and its major dipeptides, including leucine‑glycine (LG) and glycine‑leucine (GL). The anti‑fatigue effects of orally administered DPP, LG and GL were determined using a treadmill exercise test and a forced swimming test (FST) in mice. Additionally, the anti‑inflammatory effects of DPP, LG and GL were investigated in activated splenocytes. The results demonstrated that oral treatment of mice with DPP, LG and GL increased the time to exhaustion during treadmill exercise. Furthermore, DPP, LG and GL enhanced the levels of dopamine, brain‑derived neurotrophic factor and phosphorylated-extracellular signal‑regulated kinase in the brains of mice with treadmill exercise‑induced exhaustive fatigue, and decreased levels of certain proinflammatory cytokines in the serum and spleen, as determined by ELISA and western blot analysis. Following treadmill exercise, commercial kits were employed to demonstrate that DPP, LG and GL reduced the levels of lactate dehydrogenase, lactate, creatine kinase, blood urea nitrogen, alanine transaminase and aspartate transaminase in the muscle and/or serum of mice. In addition, DPP, LG and GL enhanced the muscle and liver glycogen levels, catalase activity in the liver and serum superoxide dismutase activity. DPP, LG and GL also increased the proliferation of splenocytes and inhibited proinflammatory cytokine production by reducing the activation of caspase‑1 and nuclear factor‑κB in activated splenocytes, as determined by MTT assays, ELISA and western blotting, respectively. Furthermore, DPP, LG and GL reduced immobility time in the FST in mice. In conclusion, DPP may limit intensive exercise‑induced fatigue by increasing dopaminergic systems and inhibiting inflammatory responses.

Oral Administration of Glycine and Leucine Dipeptides Improves Skin Hydration and Elasticity in UVB-Irradiated Hairless Mice.

Placenta is a special organ that contains many nutrients such as growth factors, minerals, and bioactive peptides. Dipeptides of glycine and leucine are major components of porcine placenta extracts (PPE) that has been used as an alternative of human placenta extracts. In this study, we investigated whether major peptides of PPE, Glycyl-L-Leucine (Gly-Leu), L-Leucyl-Glycine (Leu-Gly), and L-Leucyl-L-Leucine (Leu-Leu), affect skin hydration and elasticity in vitro and in vivo. We found that Gly-Leu and Leu-Gly dipeptides induced the expression of transglutaminase 1 in normal human epidermal keratinocytes (NHEKs) whereas Leu-Leu dipeptides did not. Treatment with Gly-Leu or Leu-Gly significantly increased hyaluronan (HA) synthesis in NHEKs and the upregulation of hyaluronan synthase 2 (HAS2) mRNA level was confirmed. In addition, elastase activity was inhibited in NHEKs treated with Gly-Leu or Leu-Gly dipeptides. Oral administration of Gly-Leu or Leu-Gly dipeptides increased skin hydration and elasticity in UVB-irradiated hairless mice. The significant upregulation of HA in UVB-irradiated hairless mice was observed in response to oral administration of Gly-Leu or Leu-Gly. These results suggest that the major dipeptides of porcine placenta, Gly-Leu and Leu-Gly, are potentially active ingredients for skin moisturization formulations.

Solvation behavior of glycine and glycyl dipeptide in aqueous 1-butyl-3-methylimidazolium bromide ionic liquid solutions at different temperatures

Densities and speeds of sound of glycine and glycyl dipeptide (glycylglycine) in aqueous 1-butyl-3 methylimidazolium bromide, [C4mim][Br] solutions have been measured at T=(288.15, 298.15 and 308.15) K. From the experimental data of density and speed of sound, the apparent molar volumes (Vϕ), apparent molar volumes at infinite dilution (Vϕ0), apparent molar isentropic compression (Kϕ,s) and apparent molar isentropic compression at infinite dilution (Kϕ,S0) have also been determined. Further, the partial molar volumes of transfer (ΔtrVϕ0) and partial molar isentropic compression of transfer (ΔtrKϕ,S0) of glycine and glycyl dipeptide from water to aqueous [C4mim][Br] solutions were calculated to enlighten the interactions such as solute–solute, solute–solvent and solvent–solvent present in these solutions. The apparent molar expansivity (Eϕ0), Hepler's constant values ∂Eϕ0∂TP,thermal expansion coefficient (α) and hydration number (nH) have been evaluated to assist the interpretations earned from the volumetric and acoustic analysis. The Hepler's constant values were found negative for glycine and glycyl dipeptide at all concentrations of ionic liquid except at lower concentration with glycyl dipeptide. The negative sign indicates the co-solutes act a structure breaker.

Amide and Peptide Bond Formation: Interplay between Strained Ring Defects and Silanol Groups at Amorphous Silica Surfaces

The formation of amide and peptide bonds on plain amorphous silica surfaces was studied by DFT-D3 methods on cluster silica surface models involving strained Si—O rings as sources of reactivity. The amide/peptide bond-formation reaction was found to be thermodynamically and kinetically favored compared to the gas-phase processes because of the copresence of surface (SiO)2/(SiO)3 strained ring defects, resulting from the high-temperature treatment of silica, and spatially close SiOH silanol groups. Preliminary extended calculations involving ammonia and formic acid provided insights into the most promising reaction paths for amide bond formation on defective silica surfaces. These paths were also employed to study glycine dipeptide formation. The reactions proceed through two steps: (i) silica ring opening by reaction with carboxylic acids to form a Si—O—C(═O)— surface mixed anhydride (SMA) and (ii) reaction of the SMA with amines to form the amide product. The key point of the overall reaction is the syne...

Correlation between Amide-Ⅰ Spectra and Structural Features of Glycine Dipeptide

Correlation between Amide-Ⅰ Spectra and Structural Features of Glycine Dipeptide

Competing noncovalent host-guest interactions and H/D exchange: reactions of benzyloxycarbonyl-proline glycine dipeptide variants with ND3.

A combination of density functional theory calculations, hydrogen/deuterium exchange (HDX) reactions, ion mobility-mass spectrometry, and isotope labeling tandem mass spectrometry was used to study gas-phase "host-guest" type interactions of a benzyloxycarbonyl (Z)-capped proline (P) glycine (G) model dipeptide (i.e., Z-PG) and its various structural analogues with ND3. It is shown that in a solvent-free environment, structural differences between protonated and alkali metal ion (Na(+), K(+), or Cs(+))-complexed species of Z-PG affect ND3 adduct formation. Specifically, [Z-PG + H](+) and [Z-PG-OCH3 + H](+) formed gas-phase ND3 adducts ([Z-PG (or Z-PG-OCH3) + H + ND3](+)) but no ND3 adducts were observed for [Z-PG + alkali metal](+) or [Z-PG + H - CO2](+). Experimentally measured and theoretically calculated collision cross sections (CCSs) of protonated and alkali metal ion-complexed Z-PG species showed similar trends that agreed with the observed structural differences from molecular modeling results. Moreover, results from theoretical ND3 affinity calculations were consistent with experimental HDX observations, indicating a more stable ND3 adduct for [Z-PG + H](+) compared to [Z-PG + alkali metal](+) species. Molecular modeling and experimental MS results for [Z-PG + H](+) and [Z-PG + alkali metal](+) suggest that optimized cation-π and hydrogen bonding interactions of carbonyl groups in final products are important for ND3 adduct formation. Graphical Abstract ᅟ.

Quantum Chemistry Meets Spectroscopy for Astrochemistry: Increasing Complexity toward Prebiotic Molecules.

For many years, scientists suspected that the interstellar medium was too hostile for organic species and that only a few simple molecules could be formed under such extreme conditions. However, the detection of approximately 180 molecules in interstellar or circumstellar environments in recent decades has changed this view dramatically. A rich chemistry has emerged, and relatively complex molecules such as C60 and C70 are formed. Recently, researchers have also detected complex organic and potentially prebiotic molecules, such as amino acids, in meteorites and in other space environments. Those discoveries have further stimulated the debate on the origin of the building blocks of life in the universe. Many efforts continue to focus on the physical, chemical, and astrophysical processes by which prebiotic molecules can be formed in the interstellar dust and dispersed to Earth or to other planets.Spectroscopic techniques, which are widely used to infer information about molecular structure and dynamics, play a crucial role in the investigation of planetary atmosphere and the interstellar medium. Increasingly these astrochemical investigations are assisted by quantum-mechanical calculations of structures as well as spectroscopic and thermodynamic properties, such as transition frequencies and reaction enthalpies, to guide and support observations, line assignments, and data analysis in these new and chemically complicated situations. However, it has proved challenging to extend accurate quantum-chemical computational approaches to larger systems because of the unfavorable scaling with the number of degrees of freedom (both electronic and nuclear).In this Account, we show that it is now possible to compute physicochemical properties of building blocks of biomolecules with an accuracy rivaling that of the most sophisticated experimental techniques, and we summarize specific contributions from our groups. As a test case, we present the underlying computational machinery through the investigation of oxirane. We describe how we determine the molecular structure and then how we characterize the rotational and IR spectra, the most important issues for a correct theoretical description and a proper comparison with experiment. Next, we analyze the spectroscopic properties of representative building blocks of DNA bases (uracil and pyrimidine) and of proteins (glycine and glycine dipeptide analogue).Solvation, surface chemistry (dust fraction, adsorption, desorption), and inter- and intramolecular interactions, such as self-organization and self-interaction, are important molecular processes for understanding astrochemistry. Using the specific cases of uracil dimers and glycine adsorbed on silicon grains, we also illustrate approaches in which we treat different regions, interactions, or effects at different levels of sophistication.

Correction to Balanced Protein-Water Interactions Improve Properties of Disordered Proteins and Non-Specific Protein Association.

In our paper1 we did not properly acknowledge the contribution by Head-Gordon and co-workers2 (ref 41 of our manuscript). These authors used a similar modification of the mixing rules for protein–water interactions, although the correction was applied on a per-atom basis to both the characteristic distance (sigma) and energy (epsilon) parameters rather than using a single scaling factor for epsilon as we did. Head-Gordon and co-workers used extensive solvation free energy data on model organic compounds to fit their parameters, whereas we used FRET efficiencies for a single unfolded protein (cold shock protein) to estimate our scaling parameter. Overall, we reached qualitatively similar conclusions regarding the solvation free energies of force fields with Amber 943 Lennard-Jones parameters being too unfavorable, as reported previously by these authors.2 The more systematic approach of Nerenberg et al. showed a mean signed error of solvation free energies close to zero for their optimized force field.2 We would also like to make a specific correction to the sentence on page 5115, which is inaccurate: “Recently, a full parametrization of protein Lennard-Jones parameters to reproduce solvation free energies showed some promising results, but unfortunately resulted in very unstable folded proteins”. Instead, it should read as follows: “Recently, a rescaling of protein–water Lennard-Jones parameters to reproduce solvation free energies showed some promising results for correcting protein–protein interactions using concentrated solutions of glycine and leucine dipeptides. In conjunction with a 12-10 van der Waals (vdW) term to replace the standard 12-6 vdW potential to model the nonelectrostatic part of the hydrogen bonding between the backbone carbonyl oxygens and amide protons, this modification resulted in stable folded proteins.”

Kinetic Study of the Formation of Ruhemann's Purple in Micellar and Microemulsion Phases

Abstract The reaction kinetics of ninhydrine (Nin) with glycine–glycine dipeptide (Gly) was studied in aqueous solution. The same reaction was studied in micellar solutions of different surfactants such as sodium dioctylsulfosuccinate (AOT) and sodium dodecyl sulfate (SDS). The reaction was also studied in the L2 microemulsion phase of the three systems AOT/heptane/water, SDS/pentanol/heptane/water, CTAB/pentanol/heptane/water. Spectrophotometric measurements were perfomed at 570 nm. The data show that the reaction is first-order with respect to Nin and Gly in all cases. Values of the observed rate constants (k obs) increase with increasing concentration of the surfactant in micellar media. AOT was more promotional than SDS. The reaction rate in the presence of different micelles could be explained using a pseudo-phase kinetic model. Association constants of Nin and Gly with surfactant micelles are reported. Values of k obs for the reaction rates in the microemulsion phases are reported. AOT/heptane L2 microemulsion system has been clearly found as the most promotional among all the other studied systems. Association constants of Nin and Gly with surfactant in microemulsion were obtained. The rate was increased with the temperature in aqueous, micellar and microemulsion phases. The activation parameters ΔH*, ΔS* and ΔG* have also been obtained. The reaction rate in different microemulsion media is slightly increased with the change of oil (heptane &gt; hexane &gt; pentane), while co-surfactants (butanol, pentanol and hexanol) have no effect on k obs values in AOT, CTAB or SDS microemulsion.

Site Preferences of Nucleic Acid Bases Hydrogen Bonding to Glycine Dipeptide

Site Preferences of Nucleic Acid Bases Hydrogen Bonding to Glycine Dipeptide