Linker for immobilization, modification and subsequent release of oligomers with a terminal hydroxyl group
AssigneeBiosearch Technologies, Inc.
InventorMatthew H. Lyttle
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Abstract
The invention is a method which allows the attachment of an alcohol to a substrate by the use of which chemical and/or enzymatic transformations of the alcohol are facilitated, and subsequently the modified alcohol can be released, if desired, under exquistely mild conditions, after selective removal of a protecting group from an expulsion promoting amino group.
Claims15
A method for the immobilization and subsequent release of an organic hydroxylic compound, R--OH, comprising the following steps:
- i) converting the molecule R--OH into its phosphoramidite derivative R--O--P(OR')--N(R").sub.2 wherein R is a primary, secondary, or tertiary aliphatic or aromatic group which may or may not contain other functional groups;
- wherein R' is selected from the group consisting of methyl, ethyl, cyanoethyl, phenyl, chlorophenyl, and other aliphatic, branched aliphatic or aromatic groups;
- wherein R" is selected from the group consisting of methyl, ethyl, isopropyl and other linear and branched aliphatic groups;
- ii) a hydroxyl protecting group Y is selectively removed from a derivatized solid support having the structure ##STR4## where a+b is greater than 1 but less than 6, and X is a nitrogen or CH group, wherein said structure is attached to a solid support --R by a bridge group selected from the group consisting of bifunctional aliphatic, bifunctional branched aliphatic, bifunctional polyethylene glycol containing and bifunctional aromatic groups;
- iii) said phosphoramidite is attached to said hydroxyl deprotected derivatized solid support by activation with a tetrazole solution or other phosphoramidite activator solution, followed by oxidation of the phosphorus with iodine solution or other oxidant solution to produce a compound having the structure ##STR5## iv) the protecting group Z of the intermediate produced by step iii which masks the nitrogen functionality is removed selectively, and;
- v) the intermediate produced by step iv is contacted with a mildly basic buffer solution to promote intramolecular attack at phosphorus by the nitrogen to produce the compound R--OH.
A method for the release of an organic hydroxylic compound R--OH from a solid support having the structure ##STR6## where a+b is greater than 1 but less than 6, and X is a nitrogen or CH group;
- wherein said structure is attached to a solid support --R by a bridge group selected from the group consisting of bifunctional aliphatic, bifunctional branched aliphatic, bifunctional polyethylene glycol containing and bifunctional aromatic groups between X and the support --R;
- wherein R is a primary, secondary, or tertiary aliphatic or aromatic group which may or may not contain other functional groups;
- wherein R' is selected from the group consisting of methyl, ethyl, cyanoethyl, phenyl, chlorophenyl, and other aliphatic, branched aliphatic and aromatic groups comprising contacting said structure with a mildly basic buffer solution to promote intramolecular attack at phosphorus by the nitrogen to produce the compound R--OH.
Dependencies are inferred from the claim text.