Synthesis and interfacial behavior of sulfur-containing analogs of lung surfactant dipalmitoyl phosphatidylcholine

Chang, Yusuo; Wang, Zhengdong; Notter, Robert H.; Wang, Zhongyi; Qu, Long; Schwan, Adrian L.

doi:10.1016/j.bmcl.2004.10.001

Cited by 12 publications

(14 citation statements)

References 22 publications

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“…We have previously reported the high surface activity and inhibition resistance of model surfactants containing DEPN-8 or a C16:0 sulfur-containing ether analog (SO 2 -lipid) combined with 1.5% by weight of column-isolated bovine SP-B/C [30], [35]–[37]. These prior studies with purified native SP-B/C provide a proof of concept for the current work using Mini-B in a fully-synthetic binary lipid/peptide surfactant with DEPN-8.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Surface Activity of a Fully Synthetic Phospholipase-Resistant Lipid/Peptide Lung Surfactant

et al. 2007

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BackgroundThis study examines the surface activity and resistance to phospholipase degradation of a fully-synthetic lung surfactant containing a novel diether phosphonolipid (DEPN-8) plus a 34 amino acid peptide (Mini-B) related to native surfactant protein (SP)-B. Activity studies used adsorption, pulsating bubble, and captive bubble methods to assess a range of surface behaviors, supplemented by molecular studies using Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD), and plasmon resonance. Calf lung surfactant extract (CLSE) was used as a positive control.ResultsDEPN-8+1.5% (by wt.) Mini-B was fully resistant to degradation by phospholipase A2 (PLA2) in vitro, while CLSE was severely degraded by this enzyme. Mini-B interacted with DEPN-8 at the molecular level based on FTIR spectroscopy, and had significant plasmon resonance binding affinity for DEPN-8. DEPN-8+1.5% Mini-B had greatly increased adsorption compared to DEPN-8 alone, but did not fully equal the very high adsorption of CLSE. In pulsating bubble studies at a low phospholipid concentration of 0.5 mg/ml, DEPN-8+1.5% Mini-B and CLSE both reached minimum surface tensions <1 mN/m after 10 min of cycling. DEPN-8 (2.5 mg/ml)+1.5% Mini-B and CLSE (2.5 mg/ml) also reached minimum surface tensions <1 mN/m at 10 min of pulsation in the presence of serum albumin (3 mg/ml) on the pulsating bubble. In captive bubble studies, DEPN-8+1.5% Mini-B and CLSE both generated minimum surface tensions <1 mN/m on 10 successive cycles of compression/expansion at quasi-static and dynamic rates.ConclusionsThese results show that DEPN-8 and 1.5% Mini-B form an interactive binary molecular mixture with very high surface activity and the ability to resist degradation by phospholipases in inflammatory lung injury. These characteristics are promising for the development of related fully-synthetic lipid/peptide exogenous surfactants for treating diseases of surfactant deficiency or dysfunction.

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Section: Discussionmentioning

confidence: 99%

Dynamic Surface Activity of a Fully Synthetic Phospholipase-Resistant Lipid/Peptide Lung Surfactant

et al. 2007

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“…Ester-linked glycerophospholipids of the kind found in native surfactant are the primary lipids used in current synthetic exogenous surfactants. However, synthetic ether-linked lipids are now available that have direct structural analogy to lung surfactant lipids plus designed molecular behavior that enhances adsorption and spreading while maintaining very high dynamic surface tension lowering in surface films (e.g., [71,[205][206][207][208][209][210][211]). Moreover, such lipids have structural features making them resistant to phospholipases such as phospholipase A 2 , which has been implicated in the pathology of ALI/ARDS [65,[212][213][214][215][216][217][218].…”

Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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“…Sulfur-containing sn-1 phospholipids encompass a wide spectrum of biological roles ranging from synthetic lung surfactants [15] to antitumor [25,26] and anti-HIV [27][28][29][30] agents, to analogs [26,31] of the experimental anticancer drug (±)-1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine (ET-18-OCH 3 , 1) [32] and platelet activating factor (PAF) [16].…”

Section: Sulfur-containing Sn-1 Phospholipidsmentioning

confidence: 99%

“…A growing interest in the synthesis of new phospholipids has been bolstered by applications in membrane engineering [9,10], the pursuit of vehicles suitable for introducing photodegradable molecules into membranes [11], and by a general ambition to surpass the bioactivity of natural compounds [12][13][14][15][16]. Sulfur-containing glycerophospholipids and phosphonolipids are important among the collection of synthetic glycerolipids.…”

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