Conformational analysis of neuropeptide Y-[18–36] analogs in hydrophobic environments

Lazoura, Eliada; Maidonis, Ioannis; Bayer, Ernst; Hearn, Milton Thomas William; Aguilar, Mibel

doi:10.1016/s0006-3495(97)78662-4

Cited by 38 publications

(20 citation statements)

References 21 publications

(16 reference statements)

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“…First, the relationship between the hydrophobicity of peptides and their inhibition activities was considered in peptide design because a number of studies have reported that the hypocholesterolemic effect of a peptide correlates to increased hydrophobicity 31. RP–HPLC can be especially useful as a physicochemical model of biological systems because its hydrophobic environment may reasonably mimic the hydrophobic environment created, internally, by a protein 32, 33. The overall experimental peptide hydrophobicity, assessed by retention time on RP–HPLC, was compared with peptide inhibitory activity.…”

Section: Resultsmentioning

confidence: 99%

Peptide design of a competitive inhibitor for HMG‐CoA reductase based on statin structure

Pak¹,

Kim²,

Koo³

et al. 2006

Biopolymers

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This study investigates a proposed design of a peptide sequence that is based on a bioactive conformation of statins that act as the competitive inhibitors of HMG-CoA for HMGR. To bridge these heterogeneous organic compounds, a conformational aspect relating to an analysis of the flexibility of the peptide molecules and their occupied volumes was applied to the peptide design. The design criterion was formulated in terms of a proximity parameter (Pr), reflecting the probability of an active peptide conformation to approximate the statin. Through a structure-functional analysis of previously synthesized peptides and statin molecules, nine peptides were selected for the peptide library. Comparing the calculated proximity parameters, four peptides (IAVE, YAVE, IVAE, and YVAE) from the library were selected and synthesized. In vitro assays elucidated the inhibition properties for HMGR that are exhibited by these peptides. Among all peptides, YVAE showed the highest ability to inhibit HMGR. A kinetic analysis revealed that this peptide is a competitive inhibitor of HMG-CoA with an equilibrium constant of inhibitor binding (K(i)) of 15.2 +/- 1.4 microM. The calculated coefficient correlation (R) between log (IC(50)) and the inverse value of proximity parameter (1/Pr) was found to be 0.99, indicating a high degree of correlation and efficacy of the given approach in the peptide sequence design.

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Section: Resultsmentioning

confidence: 99%

Peptide design of a competitive inhibitor for HMG‐CoA reductase based on statin structure

Pak¹,

Kim²,

Koo³

et al. 2006

Biopolymers

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“…The hydrophobic lipid‐like surfaces used in RP‐HPLC have become widely used in the study of the surface‐based induction and stabilization of a range of peptides and proteins including amphipathic monomeric α‐helices, dimeric coiled coils and β‐sheet peptides (25–31). In addition, these studies have allowed quantitative analysis of the binding of these peptides to hydrophobic n ‐alkyl chains in terms of partition/hydrophobicity coefficients and stability constants, together with the thermodynamics and kinetics associated with the conformational changes which occur upon binding to hydrophobic surfaces.…”

Section: Resultsmentioning

confidence: 99%

“…Under conditions where the hydrophobic interactions are the dominant interactive force between the solutes and the immobilized ligands, a linear dependency of solute retention, log k′ , on the solvent mole fraction, ϕ , required to elute the solute from the surface can be obtained according to log k′ = log k 0 − Sϕ where the log k 0 value is the extrapolated log k′ in the absence of organic solvent ( ϕ = 0) and S is the slope of the plot of log k′ vs. ϕ over a defined k′ range. As shown in various studies (25–31), the variation in the binding properties of peptides as a consequence of conformational effects are reflected in changes in log k′ which provides a sensitive parameter to probe the conformational status of peptides during the interaction with the immobilized lipids. In addition, variation of the temperature allows further information to be gained on the effect of peptide conformation and lipid mobility on membrane interactions.…”

Section: Resultsmentioning

confidence: 99%

Measurement of the affinity of melittin for zwitterionic and anionic membranes using immobilized lipid biosensors

Lee

Mozsolits

Aguilar

2001

The Journal of Peptide Research

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We cloned the precursor of a novel peptide from a cDNA library prepared from pharyngeal tissues of the tunicate, Styela clava. Its sequence predicted a histidine-rich, amidated 23-residue peptide (FLRF(IG)SVIHGIGHLVHHIGVAL-NH2) that we named clavaspirin. A synthetic clavaspirin was prepared and it was found that it killed Gram-positive and Gram-negative bacteria, permeabilized the outer and inner membranes of Escherichia coli, lysed phosphatidylglycerol (POPG) liposomes, and was potently haemolytic towards human and bovine erythrocytes. Each of these activities was performed more effectively at an acidic pH. Circular dichroism measurements of synthetic clavaspirin revealed a largely alpha-helical structure and polarized and residue-specific FTIR spectrometry showed that its association with phospholipid membranes was influenced by pH. Peptides such as clavaspirin may equip tunicate haemocytes to mediate cytotoxicity and participate in antimicrobial defence.

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“…As a consequence, it has been shown by several studies that the log U value is a physical parameter which is highly sensitive to the conformational status of the peptide or protein upon interaction with hydrophobic surfaces [11][12][13][14][15][16]. Peptides and proteins interact with hydrophobic surfaces in an orientation-specific manner via a specific hydrophobic contact area.…”

Section: Dependence Of Binding Affinity On Organic Solventmentioning

confidence: 99%

Interaction of amphipathic peptides with an immobilised model membrane

et al. 1999

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The interaction of melittin and a truncated analogue of melittin with an immobilised phosphatidylcholine monolayer has been studied using dynamic elution techniques. The melittin analogue (21Q analogue) had five amino acids omitted from the C-terminal region of melittin. The influence of temperature and methanol concentration on the binding affinity of the two peptides was determined and compared to the binding behaviour of two control molecules N-acetyltryptophanamide and diphenylalanine. Both peptides exhibited non-linear dependence of affinity on % methanol at different temperatures, while N-acetyltryptophanamide and diphenylalanine exhibited linear behaviour. In addition, both melittin and the 21Q analogue exhibited significant band broadening under a range of experimental conditions, which was not evident for N-acetyltryptophanamide and diphenylalanine. As melittin is known to adopt a significant degree of a-helical conformation in the presence of lipids, the results suggest that melittin and the 21Q analogue adopt different conformations and orientations upon binding to the immobilised phosphatidylcholine surface. Overall, the results of this study demonstrate that the immobilised lipid monolayer provides a powerful system to rapidly assess the affinity of peptides for different lipid surfaces.

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Conformational analysis of neuropeptide Y-[18–36] analogs in hydrophobic environments

Cited by 38 publications

References 21 publications

Peptide design of a competitive inhibitor for HMG‐CoA reductase based on statin structure

Peptide design of a competitive inhibitor for HMG‐CoA reductase based on statin structure

Measurement of the affinity of melittin for zwitterionic and anionic membranes using immobilized lipid biosensors

Interaction of amphipathic peptides with an immobilised model membrane

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