Ansamycine

Ansamycins are macrocyclic , antibiotically effective natural products that are structurally characterized by a aromatic component in which non-adjacent positions by an aliphatic bridged chain to form a cyclic structure (ansa compound Phan ). One of the aliphatic-aromatic bridging points is always an amide bond .

The name goes back to Vladimir Prelog and Wolfgang Oppolzer and is derived from the Latin "ansa" ( handle , handle).

Occurrence

Ansamycins are found in Streptomyces , Nocardia and Micromonospora and have also been isolated from plant material.

Classification

The naturally occurring ansamycins can be divided depending on the type of the aromatic component ( benzene derivative / benzoquinone , Naphthalinabkömmling / naphthoquinone ) and the chain length of the aliphatic component. Around 120 representatives were identified and characterized (as of 2000). The main group is made up of the representatives of the naphthalene C ₁₇ group.

Aromatic component	Benzene		Naphthalene
Length of the "Ansa" chain	C ₁₅	C ₁₇	C ₁₇	C ₂₃	C ₉
Biogenic ansamycins	Ansamitocin Geldanamycin Herbimycin Macbecin Maytansin	Ansatrienin Cytotrienin Mycotrienin Thiazintrienomycin Trienomycin	Ansathiazin Awamycin Damavaricin Diastrovaricin Halomicin Kanglemycin Proansamycin Protorifamycin Protostreptovaricin Rifamycin Streptovaricin Tolypomycin	Actamycin Diastrovaricin Naphthomycin Naphthomycinol Naphthoquinomycin	Rubradirin Protorubradirin

In addition to the naturally occurring ansamycins, variants have also been isolated from mutant strains or produced semisynthetically .

Selected representatives:

Geldanamycin
Cytotrienin A
Maytansine
Mertansine or DM1 (semi-synthetic)
Rifampicin (semi-synthetic)

meaning

Representatives of the naphthalene-C ₁₇ group show a selective effect against bacteria by inhibiting their RNA polymerase . The rifamycins are therapeutically important. Representatives of the benzene-C ₁₅ group such as the ansamitocine and maytansine have an anti- tumor effect . The cytostatic maytansine derivative DM1 ( mertansine ) is used as an antibody-drug conjugate with trastuzumab (T-DM1, trastuzumab-emtansine) for the treatment of HER2 / neu -positive breast cancer .

literature

Descripions on main antibiotic types . In: Barrie W. Bycroft (Ed.): Dictionary of Antibiotics & Related Substances . Chapman & Hall, London, New York, 1988. S. xiv. ( limited preview in Google Book search)
S. Funayama, GA Cordell: Ansamycin Antibiotics Discovery, Classification, Biosynthesis and Biological Activities . In: Atta-ur-Rahman (Ed.): Studies in Natual Products Chemistry. Volume 23: Bioactive Natural Products (Part D) . Elsevier, Amsterdam, 2000. ( limited preview in Google book search)
A. Stratmann: The biology of the ansamycins: example rifamycin. Anbics Laboratories AG, Martinsried. In: BIOspektrum, Volume 10 (2004), Edition 3, p. 249 ( PDF )

Individual evidence

↑ I. Krop, EP Winer: Trastuzumab Emtansine: A Novel Antibody-Drug Conjugate for HER2-Positive Breast Cancer. In: Clinical Cancer Research. 20, 2014, p. 15, doi : 10.1158 / 1078-0432.CCR-13-0541 .

[1] I. Krop, EP Winer: Trastuzumab Emtansine: A Novel Antibody-Drug Conjugate for HER2-Positive Breast Cancer. In: Clinical Cancer Research. 20, 2014, p. 15, doi : 10.1158 / 1078-0432.CCR-13-0541 .