Warren William Mccomas

Oligomer synthesis and DNA/RNA recognition properties of a novel oligonucleotide backbone analog: Glucopyranosyl nucleic amide (GNA)

Abstract A general solid phase synthesis is described for the construction of novel amide linked oligonucleotide analogs having the glucopyranosyl configuration via solid phase N-Fmoc-type peptide chemistry. The selective binding to DNA and RNA sequences by these oligomers is characterized by measurement of melting temperatures and related thermodynamic constants.

Convenient synthesis of 2,9-disubstituted guanines mediated by solid-supported reagents

A novel application has been developed to separate regioisomers chemoselectively using a solid-supported reagent. An N7/N9 purine regioisomer mixture was purified using aluminum oxide/H+ to provide the N9 isomer selectively as a parallel or high-throughput format (chemoselective high-throughput purification). 2,9-Disubstituted guanines were conveniently prepared by this new method in conjunction with solid-supported reagents.

Potent, selective MCH-1 receptor antagonists.

This paper describes the lead optimization of a new series of potent, selective, orally bioavailable, brain-penetrant MCH-1 receptor antagonists. A major focus of the work was to achieve a selectivity profile appropriate for in vivo efficacy studies and safety.

Chemoselective high-throughput purification mediated by solid-supported reagents: its application to the first 6, 9-disubstituted purine library synthesis.

A new application of solid-supported reagents was developed to separate the alkylated N7/N9 regioisomers derived from commercially available 2-amino-6-chloropurine. Simple filtration through an alumina/H+ pad or scavenging by AG/Dowex-50W-X8 resin provides diverse N9 regioisomers selectively in moderate yields with high purities (>90%). This purification method can be conveniently used in a high-throughput format and facilitates the synthesis of a purine library without laborious regioisomer separation and aqueous work-up. The first library synthesis of 6,9-disubstituted purines is reported using the combination of this novel separation method in conjunction with polymer-supported reagents.