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M T Hearn

Publications and source records attributed to M T Hearn.

At least 163 records · Page 9Linked to original sources

Reverse phase liquid chromatography of beta-endorphins and related peptides.

Anomalous band broadening of beta-endorphin related polypeptides chromatographed on hydrophobic high performance stationary phases can be attributed to ligand induced conformational changes associated with polypeptide folding. In the presence of anionic lipids the size exclusion chromatographic behaviour of members of the beta-endorphin family also exhibits similar behaviour. These structure-retention and band broadening behaviour of these polypeptides were in accord with predictions made by hydropathy algorithms and amphipathic helix representations. These observations on surface accessibility of key amino acid residues and their interaction as a conformationally induced domains with stationary phase ligands are equally relevant to other peptidic solutes and neurotransmitters.

Amino Acid Sequence↗

General strategies in the separation of proteins by high-performance liquid chromatographic methods.

General fractionation strategies for the high-resolution purification of proteins are described. The impact of different separation parameters and resolution optimisation approaches with tandem-based systems on retention and recovery behaviour is reviewed. Procedures for the successful linkage of different chromatographic steps into a preferred sequence of operations are discussed in terms of the underlying principles and modus operandi of high-performance liquid chromatographic purification of proteins and related biomacromolecules.

Animals↗

High-performance liquid chromatography of amino acids, peptides and proteins. LXXIII. Investigations on the relationships between molecular structure, retention and band-broadening properties of polypeptides separated by reversed-phase high-performance liquid chromatography.

The gradient retention behaviour in reversed-phase high-performance liquid chromatography of a series of polypeptides related to human beta-endorphin has been investigated using different n-alkylsilica stationary phases and 0.1% trifluoroacetic acid in water-acetonitrile as mobile phase. In particular, the influence of changes in gradient time and flow-rate on retention parameters has been assessed with five different porous octadecylsilica phases with average particle diameters of 4 microns and 6 microns. Decreasing the pore size from 30 nm to 7.3 nm resulted in decreased S and log k'o values for most solutes. The effect of changes in the gradient steepness parameter, b, on the bandwidth behaviour of these polypeptides has also been investigated. Anomalous band-broadening was observed for very steep and very shallow gradients, i.e. b greater than 0.7 or b less than 0.2. The significance of these results is discussed in relation to the presence of hydrophobic domains in the linear sequence, the probability of the formation of highly stabilised secondary structures and the possible involvement of multiple folded forms of a single solute in the chromatographic performance of these polypeptides.

Amino Acids↗

Evaluation of advanced silica packings for the separation of biopolymers by high-performance liquid chromatography. III. Retention and selectivity of proteins and peptides in gradient elution on non-porous monodisperse 1.5-microns reversed-phase silicas.

Following previous studies of the use of non-porous monodisperse 1.5-microns n-octyl- and n-octadecyl-bonded silicas in gradient elution of proteins, this work was aimed at elucidating further the properties of this novel column material for peptide and protein separations in comparison with wide-pore silicas. First, it is demonstrated that with short columns (e.g., 35 X 8 mm I.D.) packed with these non-porous reversed-phase materials, mixtures of small peptides and mixtures of proteins can be very efficiently resolved. When the chain length of the bonded ligand was varied, the retention of a test set of proteins in gradient elution followed the ligand sequence C18 greater than C8 approximately C4 approximately phenyl greater than C2 under constant elution conditions, and the selectivity remained unchanged. Comparison of the S values of these proteins, as determined from evaluation of the log k' vs. phi dependences with non-porous silicas and with a LiChrospher Si 1000 C8 with identical accessible ligand surface areas per unit column volume, indicated lower values for the non-porous materials (k' = capacity factor; phi = molar fraction of organic solvent; S = slope of the plot of log k' vs. phi). The origin of this behaviour is discussed.

Caseins↗

Evaluation of advanced silica packings for the separation of biopolymers by high-performance liquid chromatography. IV. Mobile phase and surface-mediated effects on recovery of native proteins in gradient elution on non-porous, monodisperse 1.5-microns reversed-phase silicas.

The reversed-phase chromatography of proteins by gradient elution with acidic, low-ionic-strength aqueous-organic eluents is often associated with losses of the biological activity of the protein. In this study, the enzymatic activities of catalase, horseradish peroxidase and pepsin were examined under static and dynamic column conditions on non-porous, monodisperse 1.5-microns reversed-phase silicas with various n-alkyl ligands. Catalase readily lost its enzymatic activity under the influence of the acidic aqueous-organic eluents in the absence of the reversed-phase packing, whereas peroxidase was partially deactivated as a result of combined mobile phase and stationary phase effects but regained its activity on storage after elution. The enzymatic activity of pepsin was found to be very dependent on the column residence time and on the type of bonded n-alkyl ligand employed.

Catalase↗

Evaluation of advanced silica packings for the separation of biopolymers by high-performance liquid chromatography. V. Performance of non-porous monodisperse 1.5-microns bonded silicas in the separation of proteins by hydrophobic-interaction chromatography.

Non-porous monodisperse 1.5-microns silicas were allowed to react with (A) and (B) N-acetylaminopropyltriethoxysilane to generate bonded phases useful in high-performance hydrophobic-interaction chromatography (HIC). Differences in the selectivity were observed between the amide and the ether phase. Peak capacities between 10 and 30 were achieved for several proteins with the amide and ether phase packed into columns of 36 X 8 mm I.D. and elution of the proteins under chromatographic conditions in which the gradient volume, VG, was held constant by varying the gradient time between 20 and 2.5 min and the flow-rate between 0.5 and 4.0 ml/min. The S values derived from the dependences of log k' on the volume fraction of the low ionic strength buffer, phi b, were of the same magnitude as reported for porous HIC silicas and showed a dependence on the molecular weight of the protein. Using these HIC stationary phases based on non-porous 1.5-microns supports, fast separations (less than 5 min) could be carried out with high biological recoveries.

Ammonium Sulfate↗

High-performance liquid chromatography of amino acids, peptides and proteins. LXXIV. Separation of heparin-binding growth factors by reversed-phase high-performance liquid chromatography.

The separation of several immunologically related forms of the bovine brain basic heparin-binding growth factor by reversed-phase high-performance liquid chromatography is described. With Bakerbond C4 reversed-phase columns, it is possible to resolve the 0.8-1.0 M sodium chloride and the 1.0-1.3 M sodium chloride components from the preceding heparin-Sepharose affinity chromatographic step in the purification procedure for these polypeptide mitogens into multiple active forms, all of which exhibit similar molecular weights and immunoreactivity with specific polyclonal antisera. Structural characterisation suggests that it is likely that these forms represent different stages in the post-translational processing of these polypeptide mitogens.

Amino Acids↗

High-performance liquid chromatography of amino acids, peptides and proteins. LXXV. Isolation of isohormones of bovine thyrotropin and lutropin.

Purification of bovine thyrotropin and lutropin by conventional soft-gel chromatographic methods is shown to yield microheterogeneous products. High-performance ion-exchange chromatography (HPIEC) can be used to purify these isohormones further for investigations into the structure/function role of glycoprotein microheterogeneity. Hormonal microheterogeneity is shown to be reflected in differences in surface-accessible charged groups, as demonstrated by HPIEC, and differences in net charge, as indicated by isoelectric focusing. Optimal separation of the glycoprotein hormones, based on protein charge, can therefore be achieved by a combination of these two methods.

Amino Acids↗

High-performance liquid chromatography of amino acids, peptides and proteins. LXXXV. Separation of isoforms of the glycoprotein hormones from human pituitary extracts.

Procedures for the high-resolution separation of microheterogeneous forms of the glycoprotein hormones, lutropin, follitropin and thyrotropin, present in human pituitary extracts are described. The sequential use of preparative isoelectric focusing and ion-exchange high-performance liquid chromatography (HPLC) allows the further discrimination of the isoforms of these glycoprotein hormones, previously considered homogeneous on the basis of their electrophoretic mobility. The ability of ion-exchange HPLC stationary phases to probe for slight differences in charge asymmetry expressed on the surface of these proteins raises the possibility of their rapid purification via the tandem on-line use of the same ion-exchange support with several different elution systems. Retention maps, illustrating the basis of this approach, are described.

Amino Acids↗

Effect of mass loadability, protein concentration and n-alkyl chain length on the reversed-phase high-performance liquid chromatographic behaviour of bovine serum albumin and bovine follicular fluid inhibin.

The chromatographic behaviour of bovine serum albumin and partially purified preparations of the 58 kilodalton form of bovine follicular fluid inhibin has been investigated using two different n-alkylsilica stationary phases. In particular, the effects of mass loadability, protein concentration and loading conditions on the relative retention, peak width and recovery of these proteins have been studied over a dynamic range up to 100 mg protein per g packing material per injection. The influence of variable amounts of more abundant contaminating proteins such as bovine serum albumin in crude inhibin preparations on the chromatographic purification of trace quantities of the 58 kilodalton inhibin protein has also been examined. Based on these observations, recommendations are offered for the selection of protein loading conditions with n-alkylsilica stationary phases, particularly for the trace recovery and purification of hydrophobic proteins similar to inhibin where self-aggregation, adsorption to glass or plastic surfaces, and aberrant chromatographic behaviour on size exclusion or adsorptive chromatographic supports may occur.

Animals↗

High-performance liquid chromatography of amino acids, peptides and proteins. LXIX. Evaluation of retention and bandwidth relationships of myosin-related peptides separated by gradient elution reversed-phase high-performance liquid chromatography.

The gradient elution behaviour of ten peptide analogues encompassing the primary amino acid sequences adjacent to the serine-19 phosphorylation site of myosin light chain has been investigated using a 30-nm pore diameter n-butylsilica stationary phase and 0.1% trifluoroacetic acid-water-acetonitrile mobile phases. Quantitative expressions derived from linear solvent strength theory and general plate height theory have been used to assess the influence of gradient time and flow-rate on the relative retentions and bandwidths of these peptides. The retention behaviour of these peptide analogues was found to closely mirror the predictions of linear solvent strength gradient elution theory. Although the experimentally observed band-width changes over a conventional range of gradient conditions (i.e. tG = 30-60 min) also correlated with bandwidth changes predicted on the basis of plate theory derived for low molecular weight organic molecules, for very steep and very shallow gradients divergencies from theory were observed. The significance of these discrepancies is discussed in relation to the influence of amino acid sequence changes rather than composition of these peptide analogues. These data allow the importance of sequential effects on the chromatographic behaviour and in particular, the resolution optimisation of these closely related peptides to be evaluated.

Amino Acids↗

The iodination sites of bovine thyrotropin.

Iodination of bovine thyrotropin (TSH) using a lactoperoxidase-catalyzed labeling method at pH 5.6 results in modification of both the alpha- and beta-subunits. In particular, 3 of the 5 tyrosine residues of the alpha-subunit and 9 of the 11 tyrosine residues in the beta-subunit are accessible to surface iodination. However, the reactivity of these tyrosine residues in bovine TSH toward iodination under these enzyme-catalyzed conditions follows the order alpha-Tyr-21 much greater than alpha-Tyr-92, -93, approximately equal to beta-Tyr-45, -54 greater than beta-Tyr-74 greater than beta-Tyr-18 approximately equal to beta-Tyr-112 greater than beta-Tyr-104 approximately equal to beta-Tyr-92 greater than beta-Tyr-7 greater than beta-Tyr-77. From reversed-phase high-performance liquid chromatography tryptic mapping, leucyl aminopeptidase M digestion, and microsequence analysis, it is clear that diiodination of the tyrosine residues is not favored for the beta-subunit with the exception of beta-Tyr-7, whereas diiodination was observed with alpha-Tyr-21 and alpha-Tyr-92/93. These data on iodination sites are evaluated in terms of the known receptor binding features of iodinated bovine TSH preparations as well as in terms of the surface accessibility of these specific residues as predicted from topographical algorithms based on an analysis of hydrophilic and hydrophobic regions of the subunits. The results provide an explanation for the anomalously low bound/total tracer ratio frequently observed in radioreceptor assay procedures for TSH and suggest a basis for further evaluation of the determinant loops associated with the hormone specificity of the beta-subunit.

Amino Acid Sequence↗

Psychological characteristics of in vitro fertilization participants.

Psychological characteristics of couples attending an in vitro fertilization clinic were examined. Participants completed measures of personality, family environment, life quality, coping, and emotional status. Couples seeking in vitro fertilization exhibited specific personality traits and cohesive, supportive relationships. Unexpectedly, they reported good quality of life and freedom from anxiety and depression.

Adaptation, Psychological↗

Isolation, characterisation and tissue localisation of an N-terminal-truncated variant of fibroblast growth factor.

An additional form of basic fibroblast growth factor (FGF), possessing full biological activity, has been isolated from bovine pituitary extracts. This polypeptide mitogen exhibits an apparent molecular weight of 17,500 by SDS-PAGE and lacks the first four N-terminal amino acid residues (Pro-Ala-Leu-Pro) of a previously described FGF preparation. Polyclonal antibodies have been raised to this FGF variant and used to examine the distribution of immunoreactive FGF species in rat and bovine tissues by immunoblot procedures. In extracts of rat pituitary, kidney, spleen and liver tissues several higher molecular weight species were detected with immunoreactive 70 kDa and 27 kDa protein bands predominating whilst a 32 kDa immunoreactive protein was also present in the brain. In bovine tissues several immunoreactive proteins with molecular weights greater than 17,500 were also observed in the brain, pituitary, adrenal, ovary and serum with these immunoblot procedures. With bovine pituitary extracts, six immunoblot bands corresponding to immunoreactive proteins of molecular weights 80,000-14,200 were observed, whilst with the brain extracts four immunoblot bands and with serum eight immunoblot bands ranging from 150,000 to 14,200 were detected. With non-immune rabbit serum, no polypeptides/proteins of corresponding molecular weight could be detected with similar immunoblot procedures. The possible relationships of these immunoreactive proteins to FGF precursor forms at various stages of processing are described.

Amino Acids↗

Isolation of inhibin from ovine follicular fluid.

Two forms of inhibin with molecular weights of 65,000 and 30,000 (65 and 30 kD) were isolated from ovine follicular fluid using a combination of gel permeation chromatography, reversed-phase high-performance liquid chromatography and preparative polyacrylamide gel electrophoresis. The 65 kD form was partially purified approximately 315-fold whilst the 30 kD form was isolated as two isoforms (29 and 30 kD) of similar biological activity and in greater than 95% purity (1210-fold purification and 4.2% recoveries). On reduction the 30 kD form resolved into four components of 36, 31, 20-21 and 16 kD of which the 20-21 and 16 kD components were similar to the corresponding inhibin subunits isolated from porcine and bovine follicular fluid. The 36 kD component was established as a non-reducible inhibin-like material, based on its binding to antiserum raised against bovine 58 kD inhibin. The nature of the remaining non-reducible 31 kD component is unknown. Two NH2-terminal amino acid sequences (first 13 amino acids) identified in purified 30 kD inhibin were identical to the corresponding subunit amino acid sequences of bovine 31 kD inhibin.

Animals↗

Application of 1,1'-carbonyldiimidazole-activated matrices for the purification of proteins. IX. Dynamic multizoning effects in biospecific affinity chromatography on porous supports: evaluation of activation and ligand coupling effects with different support materials.

The activation of several porous polymeric gels and chemically bonded glycerylpropyl-silica-based packing materials with 1,1'-carbonyldiimidazole has been further investigated. The ligand coupling characteristics of these matrices following activation at low and high levels have been determined and the properties of the derived affinity chromatographic supports examined. In addition the dynamic capacities of several immobilised-ligand systems have been compared. The use of these different affinity chromatographic supports in assessing flow-rate and column residency effects is described.

Adsorption↗

High-performance liquid chromatography of amino acids, peptides and proteins. LXVII. Evaluation of bandwidth relationships of peptides related to human beta-endorphin, separated by gradient-elution reversed-phase high-performance liquid chromatography.

The bandwidths of several polypeptides related to human beta-endorphin have been investigated with different n-alkylsilica stationary phases and different elution gradients of 0.1% trifluoroacetic acid-water-acetonitrile mobile phases. In particular, we have examined the influence of changes in the gradient steepness parameter, b, on peakwidth with five different octadecylphases, chemically bonded to porous spherical silica particles of nominally 4 micron and 6 micron average particle diameter, respectively. The effect on the zone dispersion of these polypeptide solutes as the average pore diameter of the silica matrix was increased from 7.3 nm to 30 nm with stationary phases of similar ligand densities packed into columns of identical configuration has been further documented. The experimental data on solute bandwidths and peak capacities are comparable with the corresponding bandwidth and peak capacity values calculated from analytical equations, derived from the general plate height theory and from gradient elution theory. These comparisons clearly demonstrate that anomalous bandbroadening phenomena may occur when polypeptides are eluted with steep gradients, i.e. with gradients of large b values. Moreover, as the relative chromatographic residence times of beta-endorphin peptides capable of forming a C-terminal amphiphilic secondary structures is increased, i.e. as the dwell times and median capacity factors, k, for such peptides are increased, significant divergencies arise between the observed peakwidth behaviour and the behaviour predicted by analytical relationships which describe either the dependency of peak bandwidth (as 4 sigma v) on the gradient steepness parameter, b, or the dependency of peak capacity on gradient time, tG, median capacity factor, k, and the Knox parameter, C, respectively. The importance of these divergences from the predicted bandwidth and peak capacity behaviour for polypeptides separated on reversed phases, and for resolution optimisation in particular, is evaluated. These investigations thus enable further assessment of the quantitative relevance of current models that describe polypeptide zone migration under gradient elution reversed-phase chromatographic conditions in which solute-dependent slow equilibria, mediated by conformational or solvation effects, may still occur.

Amino Acids↗