Homocoenzyme B_(12)and Bishomocoenzyme B_(12):Covalent Structural Mimics for Homolyzed,Enzyme-Bound Coenzyme B_(12)

摘要

Efficient electrochemical syntheses of "homocoenzyme B_(12)"(2,Co_(beta)-(5'-deoxy-5'-adenosyl-methyl)-cob(III)alamin)and "bishomocoenzyme B_(12)"(3,Cop-[2-(5'-deoxy-5'-adenosyl)-ethyl]-cob(III)alamin)are reported here.These syntheses have provided crystalline samples of 2 and 3 in 94 and 77% yield,respectively.In addition,in-depth investigations of the structures of 2 and 3 in solution were carried out and a high-resolution crystal structure of 2 was obtained.The two homo-logues of coenzyme B_(12)(2 and 3)are suggested to function as covalent structural mimics of the hypothetical enzyme-bound "activated"(that is,"stretched" or even homolytically cleaved)states of the B_(12)cofactor.From crude molecular models,the crucial distances from the corrin-bound cobalt center to the C5' atom of the(homo)adenosine moieties in 2 and 3 were estimated to be about 3.0 and 4.4 A,respectively.These values are roughly the same as those found in the two "activated" forms of coenzyme B_(12) in the crystal structure of glutamate mutase.Indeed,in the crystal structure of 2,the cobalt center was observed to be at a distance of 2.99 A from the C5' atom of the homoadenosine moiety and the latter was found to be present in the unusual syn conformation.In solution,the organometallic moieties of 2 and 3 were shown to be rather flexible and to be considerably more dynamic than the equivalent group in coenzyme B_(12).The homoadenosine moiety of 2 was indicated to occur in both the syn and the anti conformations.