Bio-oligomer libraries and a method of use thereof

Claim 1

A method for determining the chemical structure of a bio-oligomer ligand for an acceptor molecule comprising the steps of: (a) introducing to a library of bio-oligomers attached to solid phase supports wherein each solid chase support is attached to a single wholly deprotected bio-oligomer species, an acceptor molecule of interest such that said acceptor molecule will recognize and bind to one or more solid phase support/bio-oligomer species within the library; (b) isolating a solid phase support/bio-oligomer combination that exhibits binding with the acceptor molecule; and (c) determining the chemical structure of the bio-oligomer of the solid phase support/bio-oligomer isolated in step (b).

Claim 2

A method for determining the chemical structure of a bio-oligomer ligand for an acceptor molecule comprising the steps of: (a) introducing to a library of bio-oligomers attached to solid phase supports wherein each solid chase support is attached to a single wholly deprotected bio-oligomer species, an acceptor molecule of interest such that said acceptor molecule will recognize and bind to one or more solid phase support/bio-oligomer species within the library; (b) isolating a solid phase support/bio-oligomer combination that exhibits binding with the acceptor molecule; and (c) determining the chemical structure of the bio-oligomer of the solid phase support/bio-oligomer isolated in step (b).

Claim 6

A method for determining the chemical structure of a biologically active bio-oligomer ligand comprising the steps of: (a) subdividing a bio-oligomer library comprising a multiplicity of solid phase supports, wherein a single deprotected bio-oligomer species is attached to each solid phase support, and in which the library is prepared by a method comprising repeating k times, wherein k is at least three, the steps of: (i) providing at least two aliquots of a solid phase support, in which the solid phase support comprises a linker selected from the group consisting of a selectively cleavable linker, a plurality of selectively cleavable linkers, or a combination of a non-cleavable linker and a selectively cleavable linker, by means of which the bio-oligomer can be attached covalently; (ii) separately introducing a species of subunits of the bio-oligomers to each of the aliquots of solid phase supports such that a different subunit is introduced to each aliquot, at least one of said subunits having a protecting group or a plurality of protecting groups; (iii) completely covalently coupling the subunit to the reactive sites of the solid phase support; (iv) thoroughly mixing and deprotecting the aliquots of the solid phase supports whereby a reactive site is provided; and, after repeating steps (ii) through (iv) k times, a final step of removing any protecting groups such that the deprotected bio-oligomer remains covalently attached to the solid phase supports in which the solid phase support is modified so that a portion of bio-oligomer can be released; (b) releasing a portion of the bio-oligomers from the solid phase support/bio-oligomer by cleavage of a clearable linker; (c) detecting the biological activity of the released bio-oligomer interest in situ; (d) isolating a solid phase support/bio-oligomer combination that exhibits the specific biological activity of interest; and (e) determining the chemical structure of the bio-oligomer remaining on the solid phase support/bio-oligomer isolated in step (d).

Claim 7

A method for determining the chemical structure of a biologically active bio-oligomer ligand comprising the steps of: (a) subdividing a bio-oligomer library comprising a multiplicity of solid phase supports, wherein a single deprotected bio-oligomer species is attached to each solid phase support, and in which the library is prepared by a method comprising repeating k times, wherein k is at least three, the steps of: (i) providing at least two aliquots of a solid phase support, in which the solid phase support comprises a linker selected from the group consisting of a selectively cleavable linker, a plurality of selectively cleavable linkers, or a combination of a non-cleavable linker and a selectively cleavable linker, by means of which the bio-oligomer can be attached covalently; (ii) separately introducing a species of subunits of the bio-oligomers to each of the aliquots of solid phase supports such that a different subunit is introduced to each aliquot, at least one of said subunits having a protecting group or a plurality of protecting groups; (iii) completely covalently coupling the subunit to the reactive sites of the solid phase support; (iv) thoroughly mixing and deprotecting the aliquots of the solid phase supports whereby a reactive site is provided; and, after repeating steps (ii) through (iv) k times, a final step of removing any protecting groups such that the deprotected bio-oligomer remains covalently attached to the solid phase supports in which the solid phase support is modified so that a portion of bio-oligomer can be released; (b) releasing a portion of the bio-oligomers from the solid phase support/bio-oligomer by cleavage of a clearable linker; (c) detecting the biological activity of the released bio-oligomer interest in situ; (d) isolating a solid phase support/bio-oligomer combination that exhibits the specific biological activity of interest; and (e) determining the chemical structure of the bio-oligomer remaining on the solid phase support/bio-oligomer isolated in step (d).

Claim 13

A method for determining the chemical structure of a bio-oligomer ligand for an acceptor molecule comprising the steps of: (a) introducing, to a bio-oligomer library comprising a multiplicity of solid phase supports, wherein a single deprotected bio-oligomer species is attached to each solid phase support, and which the library is prepared by a method comprising repeating k times, wherein k is at least three, the steps of: (i) providing at least two aliquots of a solid phase support said supports having a reactive site to which a species of subunit of the bio-oligomer can be covalently coupled; (ii) separately introducing a species of subunits of the bio-oligomers to each of the aliquots of solid phase supports such that a different subunit is introduced to each aliquot, at least one of said subunits having a protecting group or a plurality of protecting groups; (iii) completely covalently coupling the subunit to the reactive sites of the solid phase support; (iv) thoroughly mixing and deprotecting the aliquots of the solid phase supports whereby a reactive site is provided; and, after repeating steps (ii) through (iv) k times, a final step of removing any protecting groups such that the deprotected bio-oligomer remains covalently attached to the solid phase supports, an acceptor molecule of interest such that said acceptor molecule will recognize and bind to one or more solid phase support/bio-oligomer species within the library; (b) isolating a solid phase support/bio-oligomer combination that exhibits binding with the acceptor molecule; and (c) determining the chemical structure of the bio-oligomer of the solid phase support/bio-oligomer isolated in step (b).

Claim 14

A method for determining the chemical structure of a bio-oligomer ligand for an acceptor molecule comprising the steps of: (a) introducing, to a bio-oligomer library comprising a multiplicity of solid phase supports, wherein a single deprotected bio-oligomer species is attached to each solid phase support, and which the library is prepared by a method comprising repeating k times, wherein k is at least three, the steps of: (i) providing at least two aliquots of a solid phase support said supports having a reactive site to which a species of subunit of the bio-oligomer can be covalently coupled; (ii) separately introducing a species of subunits of the bio-oligomers to each of the aliquots of solid phase supports such that a different subunit is introduced to each aliquot, at least one of said subunits having a protecting group or a plurality of protecting groups; (iii) completely covalently coupling the subunit to the reactive sites of the solid phase support; (iv) thoroughly mixing and deprotecting the aliquots of the solid phase supports whereby a reactive site is provided; and, after repeating steps (ii) through (iv) k times, a final step of removing any protecting groups such that the deprotected bio-oligomer remains covalently attached to the solid phase supports, an acceptor molecule of interest such that said acceptor molecule will recognize and bind to one or more solid phase support/bio-oligomer species within the library; (b) isolating a solid phase support/bio-oligomer combination that exhibits binding with the acceptor molecule; and (c) determining the chemical structure of the bio-oligomer of the solid phase support/bio-oligomer isolated in step (b).