Micellar-mediated shifts of ionization constants of amino acids and peptides

The acid-base dissociation constants, K_a, of amino acids and small peptides were determined in both aqueous and micellar solutions of sodium dodecyl sulfate and cetyltrimethylammonium bromide by potentiometric and chromatographic means. The observed differences in pK_a values between micellar media and aqueous solutions ranged between 0.23 and 2.21 units. The micellar-mediated pK_a shifts can be attributed to different solute-micelle interactions, mainly hydrophobic and electrostatic forces. The implications of the change in acid-base behavior on separation selectivity in micellar liquid chromatography and micellar electrokinetic capillary chromatography are discussed.     

Synthesis of novel fullerene amino acids and their multifullerene peptides

[60]-Fullerene functionalized amino acids with 4-6 methylene spacers from α-carbon to the nitrogen atom of fulleropyrolidine and corresponding multifullerene peptides have been synthesized.     

New synthetic strategy for o-NBS protected amino acids and their use in synthesis of mono-benzylated peptides

A synthetic strategy to prepare o-NBS protected Fmoc-amino acids under mild conditions, in a rapid and efficient way, characterised by high yields and excellent purity of the final products has been developed. The o-NBS protected Fmoc-amino acids are employed in solid phase peptide synthesis to prepare peptidomimetics carrying mono-benzylated moieties on peptide side chains.     

Nucleophilicities of amino acids and peptides

The kinetics of the reactions of amino acids with stabilized diarylcarbenium ions (Ar(2)CH(+)) have been studied photometrically in aqueous solution at variable pH. In the range of 10.5 < pH < 12, the amino acids react much faster than the competing nucleophiles hydroxide and water. Though the pK(aH) values of the amino acids vary by almost four units, the nucleophilic reactivities of all primary amino groups differ by less than a factor of 4. The secondary amino group of proline is 10(2) times more reactive, and the thiolate site in cysteine exceeds the reactivities of the primary amino groups by a factor of 10(4). Nucleophilicity parameters N as defined by the correlation log k(20 degrees C) = s(N + E) have been determined in order to include amino acids into the most comprehensive nucleophilicity scales presently available, which provide a direct comparison of n-, pi-, and sigma-nucleophiles.     

Dihedral-angle dependence of the vicinal 15N,13C spin-coupling constants. A new NMR parameter for the conformational analysis of amino acids and peptides

The first successful observation of the vicinal ¹⁵N,¹³C spin-coupling constants in a series of amino acids, comprising Val, Ile, Leu and Thr, in which the α-nitrogens are fully replaced with ¹⁵N, is described. A Karplus-type dihedral-angle dependence was noted for the coupling constants between the α-nitrogen and γ-carbon nuclei which may, in turn, be applied to the conformational analysis of other amino acids and small peptides. The potential usefulness and limitation of this new parameter in such applications is briefly discussed.     

Study of the behaviour of amino acids in aqueous solution by time-domain NMR and high-resolution NMR

The study of protein hydration by time-domain NMR is complicated by the great number of interactions involved, resulting from the presence of several amino acids and the possible modifications produced by the various structures. Moreover, a good comprehension of the molecular interactions of the simple amino acids in solution is essential to elucidate the mechanism of the biological functions of proteins. Measurements of transverse relaxation rates of the protons of water (R(2) = 1/T(2)) in aqueous solutions of amino acids such as L-glycine, L-asparagine, L-arginine and L-tryptophan were carried out in order to study the effects of chemical exchange and molecular diffusion on the amplitude of R(2). The values of R(2) measured by the Carr-Purcell-Meiboom-Gill (CPMG) sequence were studied while varying the solution pH and the parameters of the CPMG sequence. The dependence of R(2) on pH and tau (inter-pulse delay between the first and the second pulses of the CPMG sequence) is interpreted in terms of chemical exchange between the protons of water and those of the labile amino acid groups. This interpretation was confirmed by the analysis of the proton spectra acquired using a 300 MHz NMR spectrometer.     

Chiral separation of amino acids and peptides by capillary electrophoresis

Chiral separation of amino acids and peptides by capillary electrophoresis (CE) is reviewed regarding the separation principles of different approaches, advantages and limitations, chiral recognition mechanisms and applications. The direct approach details various chiral selectors with an emphasis on cyclodextrins and their derivatives, antibiotics and chiral surfactants as the chiral selectors. The indirect approach deals with various chiral reagents applied for diastereomer formation and types of separation media such as micelles and polymeric pseudo-stationary phases. Many derivatization reagents used for high sensitivity detection of amino acids and peptides are also discussed and their characteristics are summarized in tables. A large number of relevant examples is presented illustrating the current status of enantiomeric and diastereomeric separation of amino acids and peptides. Strategies to enhance the selectivity and optimize separation parameters by the application of experimental designs are described. The reversal of enantiomeric elution order and the effects of organic modifiers on the selectivity are illustrated in both direct and indirect methods. Some applications of chiral amino acid and peptide analysis, in particular, regarding the determination of trace enantiomeric impurities, are given. This review selects more than 200 articles published between 1988 and 1999.     

Organophosphorus analogs of amino acids and peptides

A method for obtaining phosphorus analogs of homoproline was developed, and the complexing properties of these compounds were studied. An effective method for obtaining optically active 1-aminoalkylphosphonic acids that is based on the stereoselective enzymatic hydrolysis of their N-acyl derivatives is proposed. New approaches to the synthesis of phosphonopeptides using privalyl chloride as the condensing agent, silylated amino phosphonic acids as the amino components of peptide synthesis, and the proteinase papain as the stereoselective catalyst for the formation of the peptide bond were developed.Institute of Bioorganic Chemistry and Petrochemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 27, No. 3, pp. 288–293, May–June, 1991. Original article submitted February 8, 1991.     

Infrared spectra of amino acids and peptides

Summary The ionization constants of glycine, glycylglycine, DL--alanine, and -alanine have been determined from their IR spectra.Khimiya Priodnykh Soedinenii, Vol. 3, No. 2, pp. 197–201, 1967     

Quantitative measurement of molecular diffusion coefficients by NMR spectroscopy

An offset-independent adiabatic inversion pulse is used in the diffusion experiment to uniformly excite a sample region that is sufficiently long to ignore the ending effects, yet is short enough to have a homogeneous RF field and to represent the pulsed field gradient with a linear approximation. Under these conditions, the diffusion decay of the peak intensity appears to be Gaussian as a function of the effective gradient field ge as if all the molecules inside the selected region experienced the same ge. Quantitative measurement of molecular diffusion coefficients is therefore made possible.     

Methyl dynamics in crystalline amino acids: MD and NMR

Correlation times for rotation of deuterated methyls in crystalline leucine, valine, and cyclo-L-alanyl-L-alanine are calculated with molecular dynamics and compared with NMR data. The simulations distinguish between methyls having different steric environments in the crystal, yielding correlation times differing by a factor of up to 30 for methyls within a given crystal. MD and NMR correlation times agree to within a factor of 2. However, averaging over nonequivalent methyls can yield correlation functions that, although actually multiexponential, are well fit by single exponentials. This may have significance for interpreting NMR data; previous NMR data did not distinguish between the methyls in these crystals. Adiabatic rotational barriers calculated with the X-ray structure differ from effective barriers during simulation by up to +/-1 kcal/mol; the difference indicates that dynamical effects have a significant role in determining rotational correlation times.     

15N NMR studies of amino acids and their reaction products with formaldehyde

Natural abundance ¹⁵N NMR spectroscopy has been used to investigate the effect of pH on the ¹⁵N chemical shifts of lysine and of ε-hydroxymethyllysine. A computer calcualtion which fits the chemical shifts of both α-and ε-nitrogen atoms versus pH has been used to predict the pK_a values. ¹⁵N chemical shifts and some ¹J(¹⁵NH) values of some other amino acids and of their reaction products with formaldehyde are also reported.     

QSAR modeling and design of cationic antimicrobial peptides based on structural properties of amino acids

Drug resistance to existing antibiotics poses alarming threats to global public health, which inspires heightened interests in searching for new antibiotics, including antimicrobial peptides (AMPs). Accurate prediction of antibacterial activities of AMPs may expedite novel AMP design and reduce the costs and efforts involved in laboratory screening. In the present study, a novel quantitative prediction method of AMP was established by quantitative structure-activity relationship (QSAR) modeling based on the physicochemical properties of amino acids. The indices of these physicochemical properties were used to define AMP. The structural variables were optimized by stepwise regression (STR). Three series of AMPs from the QSAR model were constructed by multiple linear regressions (MLR). These QSAR models showed good performance in reliability and predictability. The normalized regression coefficients of the QSAR model and the contribution of amino acids at each position of AMP may determine the suitableness of a particular residue at any given position. QSAR models constructed by STR-MLR should prove to be useful tools in peptide design with respect to the calculation, explanation, good and reliable performance, and definition of physiochemical properties.     

Stability constants of amino acids, peptides, proteins, and other biomolecules determined by CE and related methods: recapitulation of published data

The stability (affinity, association, binding, complexation, formation) constant characterizes binding interaction between the analyte and the complexing agent. Knowledge of the stability constant makes possible the prediction and estimation of the binding behavior of constituents (amino acids, peptides, proteins, drugs, antibiotics, enzymes, enantiomers) to their partners, and the finding of a suitable partner for the given analyte to form a stable complex. The present paper summarizes the stability constant determination methods and the approaches used to evaluate the experimental data. Further, the paper recapitulates the published stability constant values determined, mainly, by capillary electrophoretic methods, taken from the Web of Science database covering the last decade. Details of the experimental conditions employed for the determination of the stability constants are also given. The review attempts to give a critical evaluation of the problems that accompany the determination of stability constant and discusses their solution.     

Preparation of hydrazides of amino acids and peptides

A new method of synthesizing hydrazides of amino acids and peptides is considered which involves the hydrazinolysis of the silyl esters of the corresponding compounds. A number of hydrazides of derivatives of amino acids and peptides has been obtained in high purity with yields close to quantitative. The physicochemical characteristics of the compounds synthesized are given.All-Union Scientific-Research Institute of the Technology of Blood Substitutes and Hormones Preparations, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 684–686, September–October, 1979.     

Preparation of hydrazides of amino acids and peptides

A new method of synthesizing hydrazides of amino acids and peptides is considered which involves the hydrazinolysis of the silyl esters of the corresponding compounds. A number of hydrazides of derivatives of amino acids and peptides has been obtained in high purity with yields close to quantitative. The physicochemical characteristics of the compounds synthesized are given.