Process for the enzymatic synthesis of nucleosides
First Claim
Patent Images
1. An essentially irreversible process for synthesizing nucleosides comprising:
- (a) reacting in an essentially irreversible manner, in solution and in the presence of a nucleoside-forming enzyme (i) a first nucleoside comprising a first modified heterocyclic base, that has been modified with a substituent selected from the group consisting of alkyl, alkylphenyl, hydroxy alkyl, and hydroxy alkylphenyl substituents, bonded to a glycosyl component with (ii) a second unmodified heterocyclic base, the first modified heterocyclic base, when dissociated from the glycosyl component of the first nucleoside, providing a relatively poor substrate for the nucleoside-forming enzyme as compared to the second unmodified heterocyclic base, for a time sufficient to enable the first nucleoside to donate the glycosyl component in an essentially irreversible manner for bonding with the second unmodified heterocyclic base;
(b) yielding a mixture that includes (i) a second nucleoside comprising the second unmodified heterocyclic base bonded to the glycosyl component and (ii) the first modified heterocyclic base that has been dissociated from the glycosyl component, and(c) isolating the resulting second nucleoside from the mixture.
1 Assignment
0 Petitions
Accused Products
Abstract
A process for synthesizing nucleosides is disclosed. The process includes the reaction of an alkylated nucleoside (such as 7-methylguanosine or 7-methylinosine) with a heterocyclic base (such as adenine, 3-deazaadenine or 1,2,4-triazole-3-carboxamide) in the presence of a nucleoside-forming enzyme to form a nucleoside that includes a glycosyl component, donate by the alkylated nucleoside, bonded to the heterocyclic base.
-
Citations
19 Claims
-
1. An essentially irreversible process for synthesizing nucleosides comprising:
-
(a) reacting in an essentially irreversible manner, in solution and in the presence of a nucleoside-forming enzyme (i) a first nucleoside comprising a first modified heterocyclic base, that has been modified with a substituent selected from the group consisting of alkyl, alkylphenyl, hydroxy alkyl, and hydroxy alkylphenyl substituents, bonded to a glycosyl component with (ii) a second unmodified heterocyclic base, the first modified heterocyclic base, when dissociated from the glycosyl component of the first nucleoside, providing a relatively poor substrate for the nucleoside-forming enzyme as compared to the second unmodified heterocyclic base, for a time sufficient to enable the first nucleoside to donate the glycosyl component in an essentially irreversible manner for bonding with the second unmodified heterocyclic base; (b) yielding a mixture that includes (i) a second nucleoside comprising the second unmodified heterocyclic base bonded to the glycosyl component and (ii) the first modified heterocyclic base that has been dissociated from the glycosyl component, and (c) isolating the resulting second nucleoside from the mixture. - View Dependent Claims (2, 3, 4)
-
-
5. An essentially irreversible process for synthesizing nucleosides comprising:
-
(a) reacting in an essentially irreversible manner, in solution and in the presence of a nucleoside-forming enzyme (i) an alkylated nucleoside comprising an alkylated heterocyclic base, that has been modified with an alkyl substituent, bonded to a glycosyl component with (ii) a heterocyclic base for a time sufficient to enable the alkylated nucleoside to donate the glycosyl component in an essentially irreversible manner for bonding with the heterocyclic base to yield a mixture that includes a nucleoside comprising the heterocyclic base bonded to the glycosyl component; and (b) isolating the resulting nucleoside from the mixture. - View Dependent Claims (6, 7, 8, 9, 10, 11, 12)
-
-
13. An essentially irreversible process for synthesizing nucleosides comprising:
-
(a) reacting in an essentially irreversible manner, in solution and in the presence of a nucleoside phosphorylase enzyme and an effective amount of a phosphate (i) a first nucleoside comprising a first modified heterocyclic base, that has been modified with a substituent selected from the group consisting of alkyl, alkylphenyl, hydroxy alkyl, and hydroxy alkylphenyl substituents, bonded to a glycosyl component with (ii) a second unmodified heterocyclic base, the first modified heterocyclic base, when dissociated from the glycosyl component of the first nucleoside, providing a relatively poor substrate for the nucleoside-forming enzyme as compared to the second unmodified heterocyclic base, for a time sufficient to enable the first nucleoside to donate the glycosyl component in an essentially irreversible manner, for bonding with the second unmodified heterocyclic base; (b) yielding a mixture that includes (i) a second nucleoside comprising the second unmodified heterocyclic base bonded to the glycosyl component and (ii) the first modified heterocyclic base that has been dissociated from the glycosyl component; and (c) isolating the resulting second nucleoside from the mixture. - View Dependent Claims (14, 15, 16)
-
-
17. A process for synthesizing nucleosides comprising:
-
(a) reacting in solution and in the presence of a nucleoside phosphorylase enzyme and an effective amount of a phosphate (i) a first nucleoside, selected from the group consisting of a methylguanosine and a methylinosine, with (ii) a heterocyclic base, selected from the group consisting of adenine, deazaadenine, and 1,2,4-triazole-3-carboxamide, for a time sufficient to enable the first nucleoside to donate a ribose component for bonding with the heterocyclic base to yield a mixture that includes a second nucleoside comprising the heterocyclic base bonded to the ribose component; and (b) isolating the resulting second nucleoside from the mixture. - View Dependent Claims (18, 19)
-
Specification