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M Iqbal

Publications and source records attributed to M Iqbal.

At least 145 records · Page 8Linked to original sources
PubMed1987

Studies of synthetic peptide analogs of the amphipathic helix. Effect of charge distribution, hydrophobicity, and secondary structure on lipid association and lecithin:cholesterol acyltransferase activation.

Four peptides capable of forming an amphipathic alpha-helix have been synthesized and their conformational and lipid-binding properties studied. These peptides have been designed to vary the alpha-helix-forming potential as well as the charge distribution of the model peptide. The resulting peptide analogs and their complexes with dimyristoyl phosphatidylcholine were studied by using right angle light scattering, negative stain electron microscopy, nondenaturing gradient gel electrophoresis, circular dichroism, intrinsic tryptophan fluorescence, and differential scanning calorimetry techniques. The four analogs, [Glu4,9, Leu11,17] (reverse-18A, [Glu4,9, Leu5,11,17] reverse-18A, [Glu1,8, Leu11,17] 18A, and [Glu1,8, Leu5,11,17] 18A were derived from a model amphipathic peptide Asp-Trp-Leu-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe (18A) whose lipid-associating properties strongly mimic apolipoprotein A-I or derived from Lys-Trp-Leu-Asp-Ala-Phe-Tyr-Lys-Asp-Val-Ala-Lys-Glu-Leu-Glu-Lys-Ala-Phe (reverse-18A), a peptide with little affinity for lipid and having a reversed charge distribution compared to the 18A peptide. We have shown that by substituting glutamic acid and leucine for aspartic acid and alanine, respectively, in a weak lipid-associating amphipathic helix peptide, the lipid-associating ability can be increased. Thus, peptides with both kinds of charge distribution can associate with the lipid. The ability of the peptide to disrupt phospholipid bilayers, however, is higher for 18A analogs compared to the reverse-18A analogs even after increasing the helix-forming potential and hydrophobicity. In addition to forming smaller lipoprotein particles, the modified 18A analogs were much superior to the modified reverse-18A analogs in their ability to activate the enzyme lecithin:cholesterol acyltransferase. This demonstrates that the positions of charged residues in the amphipathic helix play an important role in lecithin:cholesterol acyltransferase activation.

Circular Dichroism↗
PubMed1985

Carbon-13 NMR relaxation studies demonstrate an inverse temperature transition in the elastin polypentapeptide.

Carbon-13 NMR longitudinal relaxation time and line-width studies are reported on the coacervate concentration (about 60% water by weight) of singly carbonyl carbon enriched polypentapeptides of elastin: specifically, (L-Val1-L-[1-13C]Pro2-Gly3-L-Val4-Gly5)n and (L-Val1-L-Pro2-Gly3-L-Val4-[1-13C]Gly5)n. On raising the temperature from 10 to 25 degrees C and from 40 to 70 degrees C, carbonyl mobility increases, but over the temperature interval from 25 to 40 degrees C, the mobility decreases. The results characterize an inverse temperature transition in the most fundamental sense of temperature being a measure of molecular motion. This transition in the state of the polypentapeptide indicates an increase in order of polypeptide on raising the temperature from 25 degrees C to physiological temperature. This fundamental NMR characterization corresponds with the results of numerous other physical methods, e.g., circular dichroism, dielectric relaxation, and electron microscopy, that correspondingly indicate an increase in order of the polypentapeptide both intramolecularly and intermolecularly for the same temperature increase from 25 to 40 degrees C. Significantly with respect to elastomeric function, thermoelasticity studies on gamma-irradiation cross-linked polypentapeptide coacervate show a dramatic increase in elastomeric force over the same interval that is here characterized by NMR as an inverse temperature transition. The temperature dependence of mobility above 40 degrees C indicates an activation energy of the order of 1.2 kcal/mol, which is the magnitude of barrier expected for elasticity.

Amino Acid Sequence↗
PubMed1984

Conformationally constrained chemotactic peptide analogs of high biological activity.

The stereochemically constrained chemotactic peptide analogs, formylmethionyl-alpha-aminoisobutyryl-phenylalanine (formyl-Met-Aib-Phe-OH) and formylmethionylcycloleucinylphenylalanine (formyl-Met-Cyl-Phe-OH) are highly effective in inducing lysosomal enzyme release from rabbit neutrophils. NMR studies of the Aib2 analog in (CD3)2SO favor a folded conformation in which the Phe NH group is inaccessible to solvent. Intramolecularly hydrogen-bonded conformations involving a Met-Aib-beta-turn or a gamma-turn centered at Aib2 are considered. The results suggest that folded conformations may allow highly active interactions with the neutrophil formylpeptide receptor.

Animals↗
PubMed1982

The helical conformations of 14- and 16-residue fragments of suzukacillin, a membrane channel-forming polypeptide.

The suzukacillin fragments, Boc-Ala-Aib-Aib-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (14), Boc-Ala-Aib-Ala-Aib-Aib-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (16G) and the completely apolar 16-residue peptide in which the glutamine residue has been replaced by alanine (16A) have been studied by 270 MHz 1H-HMR, in C2HCl3 and (C2H3)2SO solution. Intramolecularly hydrogen-bonded NH groups have been identified by temperature and solvent dependence of chemical shifts. Peptides 14 and 16A adopt folded 3(1)) helical conformations stabilized by 11 and 13 hydrogen bonds, respectively. In peptide 16G there are 12 intramolecular hydrogen bonds, with the glycine NH being solvent-exposed, in contrast to 14 and 16A.

Amino Acid Sequence↗
PubMed1981

Membrane channel forming polypeptides. 270-MHz proton magnetic resonance studies of the aggregation of the 11-21 fragment of suzukacillin in organic solvents.

270-MHz 1H NMR studies of the 11-21 suzukacillin fragment Boc-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-G) and its analogue Boc-Ala-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-A) have been carried out in CDCl3 and (CD3)2SO. The NH chemical shifts and their temperature coefficients have been measured as a function of peptide concentration in both solvents. It is established that replacement of Gln by Ala is without effect on backbone conformation. Both peptides adopt highly folded 310 helical conformations stabilized by seven intramolecular 4 leads to hydrogen bonds. Nonlinear temperature dependences are demonstrated for free NH groups in the Gln(1) peptide. Aggregation is mediated by intermolecular hydrogen bonds formed by solvent-exposed NH groups. A major role for the Gln side chain in peptide association is suggested by differences in the NMR behavior of the Gln(1) and Ala(1) peptides. For the Gln(1) peptide in CDCl3, the carboxamide side chain carbonyl group forms an intramolecular hydrogen bond to the peptide backbone, while the trans side chain NH shows evidence for intermolecular interactions. In (CD3)2SO, the cis carboxamide NH is involved in intermolecular hydrogen bonding. The possible role of the central Gln residue in stabilizing aggregates of peptide channel formers is discussed, and a model for hexameric association is postulated.

Amino Acid Sequence↗
PubMed1981

Membrane channel forming polypeptides. 270-MHz hydrogen-1 nuclear magnetic resonance studies on the conformation of the 11-21 fragment of suzukacillin.

270-MHz 1H NMR studies on the synthetic suzukacillin fragments Boc-Leu-Aib-Gly-Leu-Aib-OMe (13-17), Boc-Gln-Aib-Leu-Aib-Gly-Leu-Aib-OBz (11 -17), Boc-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (13-21), and Boc-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-OMe (11-21) have been carried out in CDCl3 and (CD3)2SO. The intramolecularly hydrogen-bonded amide hydrogens in these peptides have been identified by using solvent titration experiments and temperature coefficients of NH chemical shifts in (CD3)2SO. The peptides are shown to favor conformations stabilized by intramolecular 4 leads to 1 hydrogen bonds. The 11-21 fragment adopts a highly folded, largely 310 helical conformation stabilized by seven intramolecular hydrogen bonds. An eighth NH group [Gly(5)] appears to be involved in a weaker interaction. Evidence for the possible participation of the Gln side-chain carboxamide group in hydrogen bonding to the peptide backbone is also presented.

Amino Acid Sequence↗
PubMed1981

1H N.M.R. studies of protected alpha-aminoisobutyric acid containing peptides. Chemical shift nonequivalence of benzyloxycarbonyl methylene protons.

The benzylic methylene protons in a large number of benzyloxycarbonyl alpha-aminoisobutyric acid (Z-Aib) containing peptides, show chemical shift nonequivalence. The magnitude of the geminal nonequivalence is correlated with the involvement of the urethane carbonyl group, in an intramolecular hydrogen bond. Studies of the model compounds Z-Aib-Aib-Ala-NHMe, and Z-Aib-Aib-Aib-Pro-OMe clearly establish the presence of intramolecular hydrogen bonds, involving the urethane CO group. In both compounds marked anisochrony of the benzylic methylene protons is demonstrated. In Z-Aib-Aib-Pro-OMe, where a 4 leads to 1 hydrogen bonded beta-turn is not possible, the benzylic-CH2-protons appear as a singlet in CDCl3 and have a very small chemical shift difference in (CD3)2SO. The observation of such nonequivalence is of value in establishing whether the amino terminal Aib-Pro beta-turn is retained in large peptide-fragments of alamethicin.

Aminoisobutyric Acids↗
PubMed1978

Hypercalciuria related to cadmium exposure.

A work force has been investigated for possible cadmium intoxication. One group who are coppersmiths have an 18.5 per cent prevalence of upper urinary tract stone disease associated with a statistically highly significant hypercalciuria and reduced serum inorganic phosphate. Proof of exposure to cadmium has been confirmed in all workers. The trace element cadmium should be kept in mind when investigating stone formers who exhibit an unexplained hypercalciuria.

Cadmium↗
PubMed1977

The effect of Procion Blue on certain metabolic activities of Streptococcus mutans.

Metabolic activities of S mutans were selectively affected by Procion Blue, known to cause covalent bonds and stable cross links in relation to carbohydrate and protein. In this study, despite the reduction in extra polysaccharide, the level of activity of glucosyltransferase was not significantly changed from the control level and colonial morphology was not transformed from smooth to rough. The results of the investigation imply at least interference with formation of extra cellular polysaccharide, possibly in the bacterial cell wall.

Bacteriological Techniques↗