Process for preparing peptide derivatized oligomeric compounds
First Claim
Patent Images
1. A method for preparing a peptide linked oligomeric compound comprising the steps of:
- (a) providing a support medium derivatized with a compound wherein said compound comprises a protected hydroxyl group;
(b) treating said protected hydroxyl group with a deprotecting reagent effective to deprotect said hydroxyl group;
(c) reacting said deprotected hydroxyl group with a nucleoside having a protected hydroxyl group and an activated phosphorus containing substituent group thereby forming an extended compound;
(d) optionally treating said extended compound with a capping agent to form a capped compound;
(e) optionally repeating steps (b), (c) and (d) to form a further extended compound;
(f) treating said capped compound or said further extended compound with an oxidizing reagent thereby forming an oxidized compound comprising one or more nucleosides;
(g) repeating steps (b), (c), (d), (e) and (f) for oxidized compounds comprising one nucleoside or optionally repeating steps (b), (c), (d), (e) and (f) for oxidized compounds comprising more than one nucleoside to give a further oxidized compound;
(h) cleaving said oxidized compound or said further oxidized compound from the support medium to give said oligomeric compound comprising a linking moiety. (i) treating said linking moiety attached to said oligomeric compound with reagents effective to form a reactive sulfur moiety on said linking moiety; and
(j) reacting said reactive sulfur moiety with a peptide wherein said peptide is functionalized with a functional group reactive with said sulfur moiety thereby forming said eptide linked oligomeric compound.
2 Assignments
0 Petitions
Accused Products
Abstract
Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.
-
Citations
31 Claims
-
1. A method for preparing a peptide linked oligomeric compound comprising the steps of:
-
(a) providing a support medium derivatized with a compound wherein said compound comprises a protected hydroxyl group;
(b) treating said protected hydroxyl group with a deprotecting reagent effective to deprotect said hydroxyl group;
(c) reacting said deprotected hydroxyl group with a nucleoside having a protected hydroxyl group and an activated phosphorus containing substituent group thereby forming an extended compound;
(d) optionally treating said extended compound with a capping agent to form a capped compound;
(e) optionally repeating steps (b), (c) and (d) to form a further extended compound;
(f) treating said capped compound or said further extended compound with an oxidizing reagent thereby forming an oxidized compound comprising one or more nucleosides;
(g) repeating steps (b), (c), (d), (e) and (f) for oxidized compounds comprising one nucleoside or optionally repeating steps (b), (c), (d), (e) and (f) for oxidized compounds comprising more than one nucleoside to give a further oxidized compound;
(h) cleaving said oxidized compound or said further oxidized compound from the support medium to give said oligomeric compound comprising a linking moiety. (i) treating said linking moiety attached to said oligomeric compound with reagents effective to form a reactive sulfur moiety on said linking moiety; and
(j) reacting said reactive sulfur moiety with a peptide wherein said peptide is functionalized with a functional group reactive with said sulfur moiety thereby forming said eptide linked oligomeric compound. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 25, 26, 29)
-
-
24. A method for preparing a peptide linked oligomeric compound having one of the formulas:
-
27. A method for the large scale synthesis of a peptide linked oligomeric compound comprising the steps of:
-
(a) providing a support medium derivatized with a compound wherein said compound comprises a protected hydroxyl group;
(b) treating said protected hydroxyl group with a deprotecting reagent effective to deprotect said hydroxyl group;
(c) reacting said deprotected hydroxyl group with a nucleoside having a protected hydroxyl group and an activated phosphorus containing substituent group thereby forming an extended compound;
(d) optionally treating said extended compound with a capping agent to form a capped compound;
(e) optionally repeating steps (b), (c) and (d) to form a further extended compound;
(f) treating said capped compound or said further extended compound with an oxidizing reagent thereby forming an oxidized compound comprising one or more nucleosides;
(g) repeating steps (b), (c), (d), (e) and (f) for oxidized compounds comprising one nucleoside or optionally repeating steps (b), (c), (d), (e) and (f) for oxidized compounds comprising more than one nucleoside to give a further oxidized compound;
(h) cleaving said oxidized compound or said further oxidized compound from the support medium to give said oligomeric compound comprising a linking moiety. (i) treating said linking moiety attached to said oligomeric compound with reagents effective to form a reactive sulfur moiety on said linking moiety; and
(j) reacting said reactive sulfur moiety with an equimolar amount of a peptide wherein said peptide is functionalized with a functional group reactive with said sulfur moiety thereby forming said peptide linked oligomeric compound.
-
-
28. A compound attached to a support medium having the formula:
- 30. A peptide linked oligomeric compound having the formula:
Specification