Secretin self-assembles and interacts spontaneously with phospholipids in vitro

Gandhi, Salil; Rubinstein, Israel; Tsueshita, Takaya; Önyüksel, Hayat

doi:10.1016/s0196-9781(01)00596-4

Cited by 14 publications

(18 citation statements)

References 18 publications

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“…All the three peptides undergo conformational transition from predominantly random coil in aqueous solution to a-helix in phospholipids [158]. It is proposed that molecular interactions between the peptides and the membrane medium protect the peptides from hydrolytic attack and enzyme degradation in vivo [159,160].…”

Section: Pituitary Adenylate Cyclase-activating Polypeptidementioning

confidence: 99%

Recognition of GPCRs by Peptide Ligands and Membrane Compartments theory: Structural Studies of Endogenous Peptide Hormones in Membrane Environment

Sankararamakrishnan

2006

Bioscience Reports

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One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of threedimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to ''Membrane Compartments Theory'', the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

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Section: Pituitary Adenylate Cyclase-activating Polypeptidementioning

confidence: 99%

Recognition of GPCRs by Peptide Ligands and Membrane Compartments theory: Structural Studies of Endogenous Peptide Hormones in Membrane Environment

Sankararamakrishnan

2006

Bioscience Reports

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“…Using optical rotatory dispersion, circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, and dynamic light scattering measurements [16][17][18][19], a variety of conformations adopted by secretin in different solution conditions were investigated. From these studies, it was concluded that the peptide has a random coil conformation in aqueous solution but transits to an ordered conformation when placing in organic solvent media, e.g., in the presence of phospholipids.…”

Section: Secretinmentioning

confidence: 99%

“…They are amphipathic and thus allow secretin molecules to aggregate as a compact symmetrical hexamer through association of the apolar helical face of individual monomers [18]. At physiological concentrations, amphipathic property of the helices also permits the peptide to interact with biomimetic phospholipids bilayers through electrostatic and hydrophobic interactions [19]. These phenomena stabilize the secretin peptide by protecting it from hydrolysis or enzymatic degradation in vivo.…”

Section: Secretinmentioning

confidence: 99%

“…The first defined region is separated into three distinct parts embracing a type II β-turn like conformation (residues 9-12), a typical α-helix (residues [12][13][14], and a lose and extended form of helix (residues [15][16][17][18][19][20], whereas the second defined region is composed of an α-helix only. Stability of this ordered structure is attributed by charge balance between two poles of the helical region.…”

Section: Pacapmentioning

confidence: 99%

“…In 50% methanol, VIP exhibits a combination of short β-turn (residues 5-8) and long α-helical (residues 8-26) structures, with residues 7-10 serving as the initiation site for helical formation [51,54]. In 25% methanol, however, this single helical region becomes non-rigid and breaks down into two irregular helices (residues 9-17 and 23-28) that is separated by a disordered hinge region (residues [18][19][20][21][22] [41,51]. These studies suggested that the extents of VIP's helicity decrease with a lower ratio of organic co-solvent, and this phenomenon may also be present in other members of the family.…”

Section: Vipmentioning

confidence: 99%

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The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System

Chu¹,

Lee²,

Siu³

et al. 2006

CNSAMC

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The secretin/PACAP/VIP superfamily contains at least ten brain-gut peptides, including secretin, pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), glucagon, glucagon-like peptide-1 (GLP-1), glucagon like peptide-2 (GLP-2), gastric inhibitory polypeptide (GIP), peptide histidine isoleucine (PHI) or peptide histidine methionine (PHM), and growth hormone-releasing hormone (GHRH). These peptides exhibit a wide tissue distribution in the peripheral systems, indicating their pleiotrophic actions in the body. Meanwhile, their functions in the central nervious system (CNS) have also been consolidated recently. For instance, most of these peptides have shown to serve as neurotransmitters, neuromodulators, neurotrophic factors, and/or neurohormones in the brain, and hence, their potential as novel CNS agents in treating neurological disorders including Autism, Alzheimer's disease, Parkinson's disease and HIV-associated neuronal cell death were recently exploited. In this article, recent progress in research of peptides in this family with particular emphasis on structures, their central functions and potential use in the treatment of neuronal diseases are reviewed.

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Peptide delivery using phospholipid micelles

Banerjee

Önyüksel

2012

WIREs Nanomed Nanobiotechnol

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Peptide based drugs are an important class of therapeutic agents but their development into commercial products is often hampered due to their inherent physico-chemical and biological instabilities. Phospholipid micelles can be used to address these delivery concerns. Peptides self-associate with micelles that serve to thwart the aggregation of these biomolecules. Self-association with micelles does not modify the peptide chemically; therefore the process does not denature or compromise the bioactivity of peptides. Additionally, many amphiphilic peptides adopt α-helical conformation in phospholipid micelles which is not only the most favorable conformation for receptor interaction but also improves their stability against proteolytic degradation, thus making them long-circulating. Furthermore, the nanosize of micelles enables passive targeting of peptides to the desired site of action through leaky vasculature present at tumor and inflamed tissues. All these factors alter the pharmacokinetic and biodistribution profiles of peptides therefore enhance their efficacy, reduce the dose required to obtain a therapeutic response and prevent adverse effects due to interaction of the peptide with receptors present in other physiological sites of the body. These phospholipid micelle based peptide nanomedicines can be easily scaled-up and lyophilized, thus setting the stage for further development of the formulation for clinical use. All things considered, it can be concluded that phospholipid micelles are a safe, stable and effective delivery option for peptide drugs and they form a great promise for future peptide nanomedicines.

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Secretin self-assembles and interacts spontaneously with phospholipids in vitro

Cited by 14 publications

References 18 publications

Recognition of GPCRs by Peptide Ligands and Membrane Compartments theory: Structural Studies of Endogenous Peptide Hormones in Membrane Environment

Recognition of GPCRs by Peptide Ligands and Membrane Compartments theory: Structural Studies of Endogenous Peptide Hormones in Membrane Environment

The Secretin/Pituitary Adenylate Cyclase-Activating Polypeptide/ Vasoactive Intestinal Polypeptide Superfamily in the Central Nervous System

Peptide delivery using phospholipid micelles

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