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β-Amyloid (Aβ) is a hydrophobic peptide that drives the pathogenesis of Alzheimer's disease (AD) due to its aberrant aggregation. Inhibition of Aβ aggregation process is one of the most promising strategies for therapeutic intervention in AD. Here, we demonstrate that sterically stabilized (PEGylated) phospholipid nanomicelles (SSM) are effective in mitigating Aβ-42 aggregation using several deterministic...
We have previously shown that self-association of human vasoactive intestinal peptide with sterically stabilized liposomes (VIP-α) alters peptide conformation from random coil in aqueous solution to α-helix. This, in turn, protects the peptide from hydrolysis and amplifies and prolongs its bioactivity. The purpose of this study was to determine whether a single, intravenous injection of low-dose human...
The purpose of this study was to determine whether all d-vasoactive intestinal peptide (VIP), an inactive optical isomer of l-VIP, modulates the vasorelaxant effects of human l-VIP and pituitary adenylate cyclase activating peptide (PACAP) 1–38, two ubiquitous and pleiotropic neuropeptides that activate VPAC 1 and VPAC 2 , two VIP subtype receptors, in the intact peripheral...
Bioactive properties of certain amphipathic peptides are amplified when self-associated with sterically stabilized micelles (SSM) composed of polyethylene glycol (PEG)-conjugated phospholipids. The purpose of this study was to determine the effects of amphipathic peptide molecular mass and PEG chain length on vasoreactivity evoked by vasoactive intestinal peptide (VIP), a 28-amino acid neuropeptide,...
Helospectin I and II, two closely related mammalian neuropeptides of the secretin/glucagons/vasoactive intestinal peptide (VIP) superfamily of peptides, are co-localized with VIP in nerve fibers surrounding vascular smooth muscle. However, the role if any, VIP receptors play in transducing the vasorelaxant effects of helospectin I and II in the intact peripheral microcirculation is uncertain. The...
The purpose of this study was to determine whether human galanin, a pleiotropic 30-amino acid neuropeptide, expresses amphipathic properties in vitro and, if so, whether these properties modulate its vasoactive effects in the intact peripheral microcirculation. We found that human galanin aggregates in an aqueous solution and forms micelles with a critical micellar concentration (CMC) of 0.4μM. In...
The purpose of this study was to determine whether intrathecal injection of aqueous (random coil) vasoactive intestinal peptide (VIP) and VIP self-associated with sterically stabilized phospholipid micelles (α-helix VIP) at the lower lumbar vertebral level modulates foot withdrawal latency to low and high rate noxious radiant skin heating in anesthetized rats. We found that intrathecal random coil...
The purpose of this study was to determine whether vasoactive intestinal peptide (VIP), a pleiotropic amphipathic peptide, interacts with rigid liposomes composed of gel phase phospholipids. We found that incubation of VIP with small unilamellar gel phase liposomes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and egg phosphatidylglycerol (ePG) for 2h at room temperature had...
Secretin, a 27-amino acid neuropeptide, is a member of the glucagon/secretin/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides that elicits transient vasodilation in vivo. The purpose of this study was to determine whether association of human secretin with sterically stabilized phospholipid micelles (SSM) amplifies the vasorelaxant effects of the peptide in the peripheral...
Secretin, a 27-amino acid neuropeptide, is a member of the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic peptides. The peptide modulates gastrointestinal and neuronal function and is currently being evaluated for the treatment of autism. However, as most peptides, it has a short circulation half-life. Previously, we have shown that VIP self-assembles in aqueous...
The purpose of this study was to determine whether association of vasoactive intestinal peptide with sterically stabilized liposomes (VIP on SSL) amplifies DNA synthesis evoked by the peptide in cultured chemically transformed hamster oral keratinocytes (HCPC-1) and, if so, whether this response in mediated, in part, by SSL-induced inactivation of neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) and...
The purpose of this study was to determine the conformation and vasorelaxant effects of vasoactive intestinal peptide (VIP) self-associated with sterically stabilized phospholipid micelles (SSM) and whether calmodulin modulates both of these processes. Circular dichroism spectroscopy revealed that VIP is unordered in aqueous solution at room temperature but assumes appreciable α helix conformation...
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