Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02079 (lysine)
 58,762 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A random copolymer of 58% L-lysine and 42% L-phenylalanine, poly(Lys58Phe42), was used as a model protein for studying the role of phenylalanine residues in protein-DNA interaction. Complexes between this copolypeptide and DNA, made by direct mixing, were studied by absorbance, circular dichroism (CD), fluorescence, and thermal denaturation. Complex formation results in an increase in absorbance, and an enhancement, red-shift, and broadening of phenylalanine fluorescence. The fluorescence enhancement is opposite to the quenching observed when a tyrosine copolypeptide is bound to DNA (R. M. Santella and H.J. Li (1974), Biopolymers 13, 1909). The positive CD band of DNA near 275 nm is reduced and red-shifted by the binding of the phenylalanine copolypeptide to a greater extent than by the tyrosine copolypeptide. Thermal denaturation of the complexes in 2.5 times 10(-4) M EDTA (pH 8.0) shows three characteristic melting bands. For complexes with calf thymus DNA, free base pairs melt at Tm,I (47-49 degrees) and copolypeptide-bound base pairs show two melting bands (Tm,II at 73-75 degrees, and Tm,III at 88 -90 degrees). Similar thermal denaturation results have been observed for complexes with Micrococcus luteus DNA. The fluorecence intensity of the complexes is greatly increased when the temperature is raised to the Tm,II region. In addition to fluorescence measurements, the effects of increasing temperature on absorption and CD spectra of the complexes were also studied. Stacking interaction between the phenylalanine chromophore and DNA bases, either partial or full intercalation, is implicated by the experimental results. Several mechanisms are proposed to describe the reaction between the copolypeptide and DNA, and thermal denaturation of the complex.
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PMID:Studies on interaction between poly(L-lysine58, L-phenylalanine42) and deoxyribonucleic acids. 117 43

The amide II vibrational CD (VCD) spectra of poly (L-glutamic acid) and poly (L-lysine) in various conformational forms and those of several proteins in H2O have been measured. Characteristic VCD patterns have been observed in the amide II region due to helix, beta-sheet, and coil conformations in polypeptides. Based on their x-ray crystal structures, the proteins studied have been assigned to six categories. Proteins in the same category give rise to similar amide II VCD. While the protein conformational type is indicated using the amide II VCD, discrimination between types is less characteristic than with the previously studied amide I' VCD in D2O.
Biopolymers 1992 Mar
PMID:Vibrational CD of the amide II band in some model polypeptides and proteins. 137 54

The carboxylate-containing homopolypeptides poly(L-glutamate) [poly(Glu)] and poly(L-aspartate) [poly(Asp)] were found to form different types of ordered structures in the presence of poly(L-lysine) [poly(Lys)]. Mixing poly(Glu) with poly(Lys) in aqueous solution at neutral pH results in the instantaneous formation of a gel-like precipitate. The secondary structure of the gel precipitate can be best described as intermolecular antiparallel beta-strands, involving the backbone amide groups, as evidenced by the presence of characteristic amide I bands in the ir spectrum at 1684 and 1612 cm-1. Mixing poly(Asp) with poly(Lys) under identical conditions results in the formation of a fine precipitate with a different morphology. Examination of the ir spectrum of the precipitate revealed that unlike poly(Glu), poly(Asp) did not yield any discrete secondary structure upon precipitation with poly(Lys). Addition of solutions containing Ca2+ or Mg2+ to the poly(Glu)/poly(Lys) aggregates resulted in complete dissolution of the gel, with the disappearance of the ir bands characteristic of the intermolecular hydrogen-bonded network. The results demonstrate the importance of salt bridges in establishing strong hydrogen bonds between the backbone amide groups. Reaggregation occurred upon heating the poly(Glu)/poly(Lys) mixture in the presence of Ca2+, but not in the presence of Mg2+ ions. In the presence of Ca2+ ions, aggregation and formation of an extended hydrogen-bonded network occurred upon heating. The aggregates formed upon heating poly(Glu)/poly(Lys) in the presence of Ca2+ were attributed solely to complexation of Ca2+ to the carboxylate groups of poly(Glu) with poly(Lys) remaining free in solution. Dissolution of the aggregate could be accomplished through addition of Mg2+ at room temperature.
Biopolymers 1992 Sep
PMID:Salt bridge induced changes in the secondary structure of ionic polypeptides. 138 49

Six cyclic peptides, designed to act as topological templates in the TASP (template assembled synthetic protein) approach in protein de novo design, were investigated employing a 100-ps, 900-K molecular dynamics conformational search. The peptides are composed of two Lys-X-Lys (X = Gly, Ala) tripeptides connected at its N- and C-terminal end by a Pro-Gly motif and a cystine bridge (I), two Pro-Gly units (II), naphthalene derivatives (III), and tetrahydronaphthalene derivatives of different stereochemistry (IV-VI). The molecular dynamics conformational search established that template I had beta-sheet like geometry. Templates II-VI showed different preferential geometries, among them, e.g., distinct preferences for type V turns in Pro-Gly containing peptides and close spatial arrangement of hydrophobic naphthalene moieties. The orientation of the lysine side chains within preferential geometries of the individual templates is analyzed and a tentative evaluation for their potential to stabilize TASP molecules of 4-helix bundle topology is given.
Biopolymers 1992 Oct
PMID:Molecular dynamics conformational search of six cyclic peptides used in the template assembled synthetic protein approach for protein de novo design. 142 Sep 59

Melittin (MLT), a 26-residue cationic (net charge +5 at pH 7.2) peptide from bee venom, is well known to be a monomeric, approximately random coil; but when its charges are reduced by titration, by acetylation (net charge +2) or succinylation (net charge -2), or by screening by salt, it goes over to tetrameric alpha-helix. The conversion is promoted by raising the peptide concentration. The tetramer is held together by hydrophobic forces. We have changed the net charge to -6 by acylation with acetylcitric anhydride (a new acylating agent); this anionic derivative forms tetrameric helix at neutral pH, without salt, and at relatively low concentration, conditions under which the cationic MLT does not become helical. Thus, a high net charge is not sufficient to prevent association and helix formation. We have synthesized an anionic melittin analogue of MLT (E-MLT; net charge -4) in which all five lysine and arginine residues are replaced with glutamate, and acetyl and succinyl derivatives of E-MLT (net charges -5 and -6). All three of these are resistant to helix formation. They require much higher NaCl or NaClO4 concentration for helix formation than does MLT. Even CaCl2, MgCl2, and spermine.4HCl are less effective in helicizing E-MLT than MLT. MLT, at pH 7.2, shows increasing helix as the peptide concentration increases (8-120 microM), but E-MLT and its acyl derivatives do not. MLT and acylated MLTs in the helical tetramer show both cold- and heat-induced unfolding, with maximum stability near room temperature. At high temperature, a significant amount of residual structure remains. Heating (to 100 degrees C) monomeric MLT (i.e., MLT at low concentration) or E-MLT results in a monotonic increase in negative ellipticity. In 1.0 M NaCl, E-MLT (at sufficiently high concentration) also shows cold and hot unfolding. The results are discussed in respect to charge-charge and charge-dipole interactions, and hydrophobic effects. E-MLT is also discussed in relation to proteins of halophilic bacteria, which have higher proportions of anionic residues than do corresponding proteins of nonhalophiles.
Biopolymers 1992 Aug
PMID:Conformational studies of anionic melittin analogues: effect of peptide concentration, pH, ionic strength, and temperature--models for protein folding and halophilic proteins. 142 Sep 81

Random copolymers of lysine and alanine, 2:1 and 1:1, were trimethylated on the lysine amino groups to quaternary ammonium groups. Methylated and unmethylated polymers were prepared with Cl- or ClO4- as the counterion. CD spectra were measured for increasing concentration of peptide without added salt, and at constant peptide concentration in increasing NaCl or NaClO4. Unmethylated peptides, as the chloride, form alpha-helix more readily than do the methylated peptides. The opposite occurs with ClO4- as counterion. The helix-promoting effect of methylated lysine residues (ClO4- counterion) is diminished by the presence of alanine, as compared with effects when lysine is the only type of residue. The effect of methylation of proteins on helix formation may depend on the types of anionic groups with which the protein may be involved.
Biopolymers 1992 May
PMID:Helix formation in methylated copolymers of lysine and alanine. 151 41

Reversed-phase high performance liquid chromatography (RP HPLC) has been found to be a convenient and powerful tool for the study of the secondary structure of peptides. Here, the ability of proline to perturb the secondary structures of peptides induced at aqueous-lipid interfaces and the induced conformation of polyproline peptides were investigated by means of RP HPLC. For these studies, four different complete sets of substitution analogues of model peptides expected to have specific induced conformations were used. In the first two studies, a single lysine was "walked" through two 18-residue polyproline sequences (one N-acetylated, the other not). In the remaining two studies, a proline was "walked" through two different sequences that had been found earlier to be induced into an alpha-helical conformation during RP HPLC (an 18-residue polyalanine sequence and the amphipathic 14-residue sequence Ac-LLKLLKKLLKKLKK-NH2). Sixty-eight individual analogues were synthesized for this study and the effect of the respective substitutions on retention times was determined. The results are consistent with the concept that, upon interaction with the C-18 of the stationary phase during RP HPLC, polyproline is induced into a type II helical conformation, polyalanine into an alpha-helical conformation, and Ac-LLKLLKKLLKKLKK-NH2 into an amphipathic alpha-helical array. In an extension of this study, the antimicrobial activities of Ac-LLKLLKKLLKKLKK-NH2 and its 18 proline substitution analogues were found to be inversely correlated with their RP HPLC retention times.
Biopolymers 1992 Jun
PMID:Perturbation of peptide conformations induced in anisotropic environments. 164 63

Infrared spectra of poly(D,L-alanine), poly(L-glutamic acid), poly(L-lysine), silk fibroin, and tropomyosin have been registered for various conformations of the polypeptide chain. Assuming additivity of the main- and side-chain absorption, spectral parameters of amide I and II absorption bands corresponding to alpha-, beta-, and random coil conformations have been derived. The amide I band parameters for H2O and D2O have been compared.
Biopolymers 1990
PMID:Quantitative IR spectrophotometry of peptide compounds in water (H2O) solutions. II. Amide absorption bands of polypeptides and fibrous proteins in alpha-, beta-, and random coil conformations. 170 90

13C-nmr measurements are reported for samples of poly (L-lysine) both static and spinning at the magic angle in the beta-sheet form as a function of water content. The addition of water decreases the side-chain line widths considerably. Measurements of the cross-polarization time constants indicate that hydration by either H2O or D2O increases the time constant. Measurements of spin-lattice relaxation times in the laboratory frame and the rotating frame indicate that hydration does not change the dynamics of the backbone carbon atoms in the beta-sheet structure appreciably, but the side-chain atoms experience considerable increase in local mobility with increasing hydration. Deuteration of the exchangeable protons or the water has only small effects on the carbon relaxation times, indicating that relaxation is driven by intramolecular dipole-dipole interactions.
Biopolymers 1991 Jul
PMID:The hydration response of poly (L-lysine) dynamics measured by 13C-NMR spectroscopy. 178 57

Natural and synthetic peptides that contain detectable intramolecular alpha-helical structure in aqueous solution have been used to evaluate the helical propensities for the common amino acids. Experimental spectroscopic data must be fit to a model of the helix-coil transition in order to determine quantitative stability constants for each amino acid. We present here a statistical mechanical description of helix formation in peptides or protein fragments that takes into account multiple internal conformations, heterogeneity in the stabilizing effects of different side chains, and specific side-chain-side-chain interactions. The model enables one to calculate values of [theta]222 for a given peptide using the length dependence of the helix signal computed by a quantum mechanical treatment of the n pi * transition that dominates the 222-nm band. In addition, the helical probability at any residue in the chain is readily computed, and should prove useful as nmr spectral data become available. The free energy of specific side-chain interactions, including ion pair formation, can be evaluated. Application of the analysis to experimental data on a pair of isomeric peptides, only one of which contains ion pairs, indicates that forming a single glutamate-lysine ion pair stabilizes the alpha-helix by 0.50 kcal/mole in 10 mM sodium ion and pH 7. A survey of the CD data measured for a variety of model peptides is presented, indicating that a single set of s values and sigma constant can account for some but not all of the available results.
Biopolymers 1991 Nov
PMID:The helix-coil transition in heterogeneous peptides with specific side-chain interactions: theory and comparison with CD spectral data. 181 7


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