Kedarcidins

In another paper, Liu et al. (30) described the interaction of hbronectin with heparin as a model system. The two distinct binding constants in the nanomolar range were derived from Scatchard plots and found in good agreement with published data. The established ACE binding assay was then applied to the molecular interaction of a kedarcidin chromophore with apoprotein. Dissociation constants in the lower micromolar range were calcu-... 

Kedarcidin is a chromoprotein anti-tumor antibiotic, produced by an actinomycete strain. It is an acidic complex with an apparent molecular weight of 12,400 Da, and it consists of an apoprotein and a cytotoxic highly unstable nonprotein chromophore 12 that possesses a conformationally defined ansamacrocyclic bridge. Retrosynthetically,... 

Another DNA-damaging antitumor agent is kedarcidin from an actinomycete which consists of an apoprotein and an enediyne chromophore (189) with a chloropyridine moiety [151,152]. 

The previously known kedarcidin chromophore (7) is revised to CCC (7559), and the mechanism of action of this enediyne has been studied (1560). The new maduropeptin chromophore 1601 was isolated from Actinomadura madurae, which is associated with a protein of 14 amino acids (1561-1563). The non-protein associated enediyne N1999A2 (1602) was characterized from Streptomyces sp. AJ 9493 (1564), and confirmed by synthesis (1565,1566). 

Kawata S, Ashizawa S, Hirama M (1997) Synthetic Study of Kedarcidin Chromophore Revised Structure. J Am Chem Soc 119 12012... 

Myers AG, Hurd AR, Hogan PC (2002) Evidence for Facile Atropisomerism and Simple (Non-Nucleophilic) Biradical-Forming Cycloaromatization within Kedarcidin Chromophore Aglycon. J Am Chem Soc 124 4583... 

Karstedt s catalyst, nickel analog, 8, 138-139 Kedarcidin, via ring-closing diene metathesis, 11, 208-209 Kendomycin, via ring-closing metathesis, 11, 239 KERD, see Kinetic energy release distribution Ketenes, niobium complexes, 5, 84 Ketenimines... 

These novel, extremely potent antibiotics all possessed one very unusual chemical structural feature an enediyne fragment within a ring. The first discovered was neocarzinostatin (NSC), which was found to be composed of a protein (NSC apoprotein) and the neocarzinostatin chromophore 30 in a 1 1 complex. The biological activity is associated with the NSC chromophore. However, it took until the discovery of the calichaemicin " 31 and esperamicin 32 families in 1987 to really gamer the broad attention of chemists. Other enediyne antibiotics include the dynemicin family, the kedarcidin chromophore, namenamicin, the C-1027 chromophore,and uncialamycin. " ... 

The anthraquinone 22, naphthalene 23a and the naphthoic acid amide 24 are respective constituents of the bacterial enediyne antibiotics dynemycin A, neocarzinostatin and kedarcidin (Scheme 5). [ C2]acetate feeding studies have established the polyketide origins of the anthraquinone nucleus 22 which is devoid of any carbon substituents and also the rare 1,8-disubstituted naphthalene 23a. ... 

Lear, M J, Yoshimura, F, Hirama, M, A direct and efficient a-selective glycosylation protocol for the kedarcidin sugar, L-ntycarose AgPFg as a remarkable activator of 2-deox)4hioglycosides, Angew. Chem. Int. Ed., 40, 946-949, 2001. 

The family of enediynes includes the calicheamicins, esperamycins, dynemicin A, which is not glycosylated, the C-1027 chromophore and kedarcidin (O Fig. 18 and Fig. 19). The neocarzinostatin chromophore, which does not contain an (Z)-enediyne, is also included in this family of compounds because of a similar mode of action. 

Myers, A.G. Hurd, A.R. Hogan, P.C. Evidence for facile atropisomerism and simple (non-nucleophilic) biradical-forming cycloaromatization within kedarcidin chromophore aglycon. J. Am. Chem. Soc. 2002, 124, 4583-4585. 

Magnus, P. Carter, R. Davies, M. Elliott, J. Pitterna, T. Studies on the synthesis of the core structures of the antitumor agents neocarzinostatin, kedarcidin, C-1027 and maduropeptin. Tetrahedron 1996, 52. 6283-6306. 

Takahashi, T. Tanaka, H. Yamada, H. Matsumoto, T. Sugiura, Y. DNA cleavage by a nine-membered masked enediyne, an analogue of the kedarcidin and C-1027 chromophores. Angew. Chem., Int. Ed. Engl. 1996, 35, 1835-1836. 

Another incorrect structure was revealed by synthetic work aimed at structure 44, alleged to be a part structure (the chromophore ) of the antitumour antibiotic kedarcidin. The synthesis was successful but revealed that the structure was wrong as the compound is a P-amino acid and not an a-amino acid as had been assumed.6... 

Kedarcidin, isolated by Zein et al. (Bristol-Myers), was first reported in 1991 as the fermentation product of a novel actinomycete strain obtained from soils collected in India [129]. It exhibits potent in-vivo antitumor activity similar to that of the other enediyne antibiotics, and pronounced activity against Gram-positive bacteria. Kedarcidin was separated relatively easily by reversed-phase HPLC into the apoprotein and chromophore components, and is found to be a varying complex depending upon fermentation conditions [28],... 

The kedarcidin apoprotein exists as three main variants [28] the major variant consists of 114 amino acid residues and a further two minor variants lack one or both of the first two amino acids (an alanine and a serine) of the major variant. Similarly, three kedarcidin chromophores have been identified having molecular weights of 1029, 1015 and 1001. Unlike the 1 1 apoprotein/chromophore ratio observed with neocarzinostatin, this ratio varies from 1 1 to 18 1 for kedarcidin. Using pilot-scale fermentations (1000 L) with fish emulsions in... 

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