Duramycin

Names

[ Name ]:
Duramycin

[Synonym ]:
UNII-BPR0F3X56H
Lancovutide [INN]
Ancovenin,2-L-lysine-6-(3-aminoalanine)-10-L-phenylalanine-12-L-phenylalanine-13-L-valine-15-(erythro-3-hydroxy-L-aspartic acid)-,cyclic 6-19)-imine
Leucopeptin
LANCOVUTIDE

Biological Activity

[Description]:

Duramycin (Moli1901;Lancovutide) is a cyclic peptide lantibiotic derived from Streptomyces cinnamoneuma. Duramycin stimulates chloride secretion in airway epithelium and has the potential for cystic fibrosis treatment. Duramycin interacts with phosphatidylethanolamine (PE) and has antibacterial, antiviral effects[1][2].

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Influenza Virus

Research Areas >> Infection

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Anti-infection >> Bacterial

[In Vitro]

Duramycin does stimulate Cl- efflux from cystic fibrosis bronchial epithelial cells (CFBE) in a narrow concentration range (around 1 μM). However, 100 and 250 μM of Duramycin inhibits Cl- efflux from CFBE cells. The [Ca2+]i is increased by 3 μM Duramycin in 16HBE cells, but decreases after 1, and 3 μM of Duramycin in CFBE cells[1]. Duramycin affects protein-lipid interactions, impairs protein translocation, induces aggregation of lipid vesicles, and inhibits ATP-dependent Ca2+ uptake by the sarcoplasmic reticulum[1].

[In Vivo]

Evaluation of [68Ga]NODAGA-Duramycin as a positron emission tomography (PET) tracer of cell death for whole-body detection of chemotherapy-induced organ toxicity. Organ uptake is analyzed in untreated and doxorubicin, busulfan, and cisplatin-treated mice 2 h after intravenous injection of [68Ga]NODAGA-Duramycin. [68Ga]NODAGA-Duramycin PET/CT is successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in mice[3].

[References]

[1]. Oliynyk I, et al. Effect of duramycin on chloride transport and intracellular calcium concentration in cystic fibrosis and non-cystic fibrosis epithelia. APMIS. 2010 Dec;118(12):982-90.

[2]. Huo L, et al. Insights into the Biosynthesis of Duramycin. Appl Environ Microbiol. 2017 Jan 17;83(3). pii: e02698-16.

[3]. Rix A, et al. Assessment of Chemotherapy-Induced Organ Damage with Ga-68 Labeled Duramycin. Mol Imaging Biol. 2019 Aug 8.

Chemical & Physical Properties

[ Density]:
1.0238 (rough estimate)

[ Melting Point ]:
271-273ºC

[ Molecular Formula ]:
C₈₉H₁₂₅N₂₃O₂₅S₃

[ Molecular Weight ]:
1999.25000

[ Exact Mass ]:
1997.82000

[ PSA ]:
835.99000

[ Index of Refraction ]:
1.6680 (estimate)

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
0.1 M HCl: soluble10mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: BV7100000

CHEMICAL NAME :: Ancovenin, 2-L-lysine-6-(3-aminoalanine)-10-L-phenylalanine-12-L -phenylalanine-13-L-v aline- 15-(erythro-3-hydroxy-L-aspartic acid)-, cyclic 6-19)-imine

CAS REGISTRY NUMBER :: 1391-36-2

LAST UPDATED :: 199801

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C89-H125-N23-O25-S3

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: JAJAAA Journal of Antibiotics, Series A. (Tokyo, Japan) V.6-20, 1953-67. For publisher information, see JANTAJ. Volume(issue)/page/year: 17,262,1964

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
BV7100000

Articles

Stimulation of sodium transport by duramycin in cultured human colonic epithelia.

J. Pharmacol. Exp. Ther. 259 , 1050, (1991)

Effects of two peptide antibiotics, duramycin and Ro 09-0198, on ion transport in cultured human colonic epithelia were investigated. Both peptides acted on the apical face of epithelial monolayers, c...

Upregulated function of mitochondria-associated ER membranes in Alzheimer disease.

EMBO J. 31 , 4106-23, (2012)

Alzheimer disease (AD) is associated with aberrant processing of the amyloid precursor protein (APP) by γ-secretase, via an unknown mechanism. We recently showed that presenilin-1 and -2, the catalyti...

Phosphatidylethanolamine is externalized at the surface of microparticles.

Biochim. Biophys. Acta 1821(12) , 1501-7, (2012)

Microparticles (MPs) are membrane-bound vesicles shed normally or as a result of various (pathological) stimuli. MPs contain a wealth of bio-active macromolecules. Aminophospholipid phosphatidylserine...