The present invention relates to novel methods and novel solid support
materials for the tandem synthesis of two or more different
oligonucleotides on the same solid support in one synthetic run. The
methods involve novel support preparations comprised of two or more types
of orthogonally protected anchor groups. Subsequent to the selective
removal of the first of the respective protective groups, the first
oligonucleotide is assembled on the deblocked anchor groups according to
standard methods, preferably via phosphoramidite chemistry. Following the
capping of said first oligonucleotide, the anchor groups blocked by a
second type of protective group are selectively liberated and serve as
the starting point for the assembly of a second oligonucleotide, and so
forth. After completion of all the syntheses on the solid support, the
oligonucleotides are released from the solid support and deprotected at
the nucleobases, using standard methods. Preparations obtained using the
method of this invention, generally contain two or more different
oligonucleotides. Such preparations are particularly useful in
applications that require pairs of oligonucleotide primers, several
probes at a time, duplexed nucleic acid fragments, or other combinations
of oligonucleotides that are useful in applications such as PCR,
sequencing, multiplexed genotyping, cloning and RNA interference. The
invention includes procedures for the preparation of the novel solid
supports of the invention.