76168-82-6

Basic information

• Product Name: Ramoplanin
• Synonyms: Ramoplanin;A 16686;A 16686A;Antibiotic A 16686;RaMoplanin(A 16686,A 16686A);RaMoplanin coMplex
• CAS NO: 76168-82-6
• Molecular Formula: C106H170ClN21O30
• Molecular Weight: 2254.0597
• Mol File: 76168-82-6.mol
• Article Data: 0

Chemical Properties

• Melting Point: 210-230°
• Appearance: /
• Storage Temp.: ?20°C
• Solubility: H2O: soluble10mg/mL
• CAS DataBase Reference: Ramoplanin(CAS DataBase Reference)
• NIST Chemistry Reference: Ramoplanin(76168-82-6)
• EPA Substance Registry System: Ramoplanin(76168-82-6)

Safety Data

• Hazard Codes: Xi
• Statements: 41
• Safety Statements: 26-39
• WGK Germany: nwg
• RTECS: VE5050000
• Hazardous Substances Data: 76168-82-6(Hazardous Substances Data)

Usage

Description

Ramoplanin is a novel oral nonabsorbable 17-amino-acid cyclic lipoglycodepsipeptide antibiotic from Biosearch Italy. It is an antibiotic complex, first identified in 1984, that was isolated from the fermentation broth of Actinoplanes sp. ATCC 33076. Ramoplanin 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. It is a potent cyclic lipoglycodepsipeptide antibiotic that exhibits a wide spectrum of antibiotic properties against gram-positive and gram-negative bacteria and acts by inhibiting cell wall biosynthesis via a different mechanism from the vancomycin-related glycopeptides.

Uses

Used in Pharmaceutical Industry:
Ramoplanin is used as an antibiotic for treating bacterial infections, particularly against gram-positive and gram-negative bacteria. Its unique mechanism of action, different from vancomycin-related glycopeptides, makes it a valuable option for combating drug-resistant strains.
Used in Research and Development:
Ramoplanin is used as a research tool for studying the mechanisms of antibiotic resistance and the development of new antibiotics. Its complex structure and unique mode of action provide insights into the development of novel antimicrobial agents.
Used in Antiviral Applications:
Ramoplanin is used as an antiviral agent, with its initial isolation in the early 1980s demonstrating antiviral and antibiotic activity against drug-resistant gram-positive isolates. This property makes it a potential candidate for further research and development in the field of antiviral therapies.
Used in Drug Resistance Studies:
Ramoplanin is used as a study subject to understand the mechanisms of drug resistance in bacteria, particularly in the context of gram-positive isolates. This knowledge can contribute to the development of strategies to combat the growing issue of antibiotic resistance.

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.

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.

InChI:InChI=1/C106H170ClN21O30/c1-8-9-10-11-15-22-80(140)114-75(50-78(110)138)96(147)118-76(51-79(111)139)97(148)124-86(60-25-36-66(133)37-26-60)102(153)117-72(21-17-46-109)92(143)120-83(56(6)130)100(151)126-89(63-31-42-69(136)43-32-63)105(156)127-88(62-29-40-68(135)41-30-62)104(155)121-82(55(5)129)99(150)119-74(48-58-18-13-12-14-19-58)95(146)116-71(20-16-45-108)93(144)123-87(61-27-38-67(134)39-28-61)103(154)122-84(57(7)131)101(152)125-85(59-23-34-65(132)35-24-59)98(149)112-52-81(141)115-73(47-53(2)3)94(145)113-54(4)91(142)128-90(106(157)158)64-33-44-77(137)70(107)49-64/h10-15,18-19,22,53-57,59-77,82-90,129-137H,8-9,16-17,20-21,23-52,108-109H2,1-7H3,(H2,110,138)(H2,111,139)(H,112,149)(H,113,145)(H,114,140)(H,115,141)(H,116,146)(H,117,153)(H,118,147)(H,119,150)(H,120,143)(H,121,155)(H,122,154)(H,123,144)(H,124,148)(H,125,152)(H,126,151)(H,127,156)(H,128,142)(H,157,158)/b11-10-,22-15-/t54-,55+,56+,57+,59?,60?,61?,62?,63?,64?,65?,66?,67?,68?,69?,70?,71-,72-,73+,74+,75+,76?,77?,82+,83-,84+,85?,86-,87?,88-,89-,90?/m1/s1