Chromophores kedarcidin

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-... 

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... 

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. " ... 

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. 

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... 

Scbeme 7-15 Proposed mechanism by which kedarcidin chromophore cleaves DNA. 

The similarities of the core enediynes of the kedarcidin and C-1027 chromophores with the neocarzinostatin chromophore structure means that many of the synthetic studies relating to NCS chromophore also, by implication, relate to the other chromoprotein enediyne antibiotics, although no examples specifically relating to these new antibiotics have appeared to date. However, a synthesis of kedarosamine, a sugar component of the kedarcidin chromophore, has appeared recently [272],... 

The mechanism of activation of the kedarcidin chromophore is thought to be similar to that of the neocarzinostatin chromophore, with nucleophilic addition at C-12 initiating epoxide opening and producing the intermediate 309. The change in stmctural geometry then facilitates the cycloaromatization reaction, leading to... 

Figure 3.92 Proposed biosynthetic pathway for the kedarcidin chromophore. (a) 1-Mycarose and kedarosamine from D-glucose-1-phosphate (b) (i )-2-aza-3-chloro-p-tyrosine from 2-aza-l-phenylalanine.

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