Ramoplanin Chemical Properties

Melting point:

210-230°

alpha 

D20 +78.3° (c = 1.04 in H2O)

storage temp. 

-20°C

solubility 

H2O: soluble10mg/mL

form 

powder

color 

White to Off-White

InChIKey

FSBZBQUUCNYWOK-KFTDLNJOSA-N

Safety Information

Hazard Codes 

Xi

Risk Statements 

41

Safety Statements 

26-39

WGK Germany 

nwg

RTECS 

VE5050000

Toxicity

LD50 in mice (mg/kg): 328 i.p., 122 i.v.; orally in rats: 2000 mg/kg (Pallanza)

Ramoplanin Usage And Synthesis

Mode of action

The lipid carrier involved in transporting the cell wall building block across the membrane is a C55 isoprenyl phosphate. The lipid acquires an additional phosphate group in the transport process and must be dephosphorylated in order to regenerate the native compound for another round of transfer. Ramoplanin as cyclic peptide antibiotics binds to the C55 lipid carrier. Ramoplanin prevents it from participating in transglycosylation thus disrupting the lipid carrier cycle.

Description

Ramoplanin (A 16686, A16686A, MDL 62198) is a novel oral nonabsorbable 17-amino-acid cyclic lipoglycodepsipeptide antibiotic from Biosearch Italy. Ramoplanin is an antibiotic complex, first identified in 1984, that was isolated from the fermentation broth of Actinoplanes sp. ATCC 33076. It is a mixture of three closely related compounds, ramoplanin A1–A3, which differ only in the acyl group attached to the Asn-1 N-terminus; ramoplanin A2 is the most abundant.

Uses

Ramoplanin is a potent cyclic lipoglycodepsipeptide antibiotic that exhibits wide spectrum of antibiotic properties against gram-positive and gram-negative bacteria.

Uses

Ramoplanin is a complex of three high molecular weight glycolipodepsipeptides, varying in the chain length and shape of the dieneone lipid side-chain. Ramoplanin was isolated in the early 1980s as the major metabolite of a strain of Actinoplanes with antiviral and antibiotic activity against drug resistant Gram positive isolates. Ramoplanin acts by inhibiting cell wall biosynthesis via a different mechanism from the vancomycin-related glycopeptides.

Antimicrobial activity

Ramoplanin displays activity against aerobic and anaerobic Grampositive bacteria by preventing cell wall peptidoglycan formation through binding to a key intermediate moiety, lipid II, and thereby disrupting bacterial cell wall synthesis. The primary use of ramoplanin is in the treatment of Clostridium difficile infections.

Mechanism of action

The mechanism of action of ramoplanin involves sequestration of peptidoglycan biosynthesis lipid intermediates, thus physically occluding these substrates from proper utilization by the latestage peptidoglycan biosynthesis enzymes MurG and the transglycosylases (TGases). Ramoplanin is structurally related to two cell wall-active lipodepsipeptide antibiotics, janiemycin and enduracidin, and is functionally related to members of the lantibiotic class of antimicrobial peptides (mersacidin, actagardine, nisin, and epidermin) and glycopeptide antibiotics. As a consequence of its unique mechanism of action, cross-resistance with existing glycopeptides and beta-lactam antibiotics has not been observed.

Pharmacokinetics

Ramoplanin is not absorbed from the intestinal tract. When ramoplanin (200 and 400 mg) was administered orally to two groups of healthy volunteers over a period of 10 days, no ramoplanin could be detected in plasma and urine. With the 200-mg dose, concentrations in stools varied between 467 and 1043 mg/g, and with the 400-mg dose, concentrations were between 765 and 2032 mg/g. Results from an in vitro gut model and hamster model revealed that ramoplanin may be more effective than vancomycin at killing spores and preventing spore recrudescence.

Toxicology

When administered orally in a double-blind randomized placebocontrolled study, no adverse reactions were observed in patients receiving two daily doses of ramoplanin (100 or 400 mg) in comparison with the placebo. Single and repeated topical application in ten healthy human volunteers revealed very low irritation rates and no sensitization after 21 days.

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