US 6,022,963 A · Synthesis of oligonucleotide arrays using photocleavable protecting groups

Abstract

Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar--C(R.sub.1)(R.sub.2)--O--C(O)-- wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R.sub.1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar--C(R.sub.1)(R.sub.2)--O--C(O)-- via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R.sub.1 =R.sub.2 =H, X is not linked to Ar--C(R.sub.1)(R.sub.2)--O--C(O)-- via a nitrogen atom. Preferred embodiments are those in which Ar is a fused polycyclic aromatic hydrocarbon and in which the substituents on Ar, R.sub.1 and R.sub.2 are electron donating groups. A particularly preferred protecting group is the "PYMOC" protecting group, pyrenylmethyloxycarbonyl, where Ar=pyrenyl and R.sub.1 =R.sub.2 =H. Also provided is a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support, using the protected compounds described above.

Claims29

Dependent claims

A method of attaching a molecule with a reactive site to a support comprising the steps of:

(a) providing a support with a reactive site;
(b) binding a molecule to the reactive site, said first molecule comprising a masked reactive site attached to a photolabile protecting group of the formula Ar--C(R.sub.1)(R.sub.2)--O--C(O)--, wherein:
Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogously substituted derivative of the foregoing;
R.sub.1 and R.sub.2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, or optionally substituted aryl or heteroaromatic group or a vinylogously substituted derivative of the foregoing;
to produce a derivatized support having immobilized thereon the molecule attached to the photolabile protecting group;
and
(c) removing the photolabile protecting group to provide a derivatized support comprising the molecule with an unmasked reactive site immobilized thereon.

4 more elements

Dependencies are inferred from the claim text.

Synthesis of oligonucleotide arrays using photocleavable protecting groups

Life of this patent

Synthesis of oligonucleotide arrays using photocleavable protecting groups

Life of this patent

Abstract

Claims29