Bio-oligomer libraries and a method of use thereof
AssigneeArizona Board of Regents
InventorsKit Sang Lam, Sydney E. Salmon
Life of this patent
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Abstract
The instant invention provides a library of bio-oligomers of defined size and known composition, in which the library contains all of the possible sequences of the bio-oligomers, and a method of synthesis thereof. The bio-oligomers of the library may be peptides, nucleic acids, or a combination of the foregoing. The instant invention also provides methods to identify bio-oligomers from a library that demonstrate desired characteristics such as binding, bioactivity and catalytic activity. Thus the instant invention provides a unique and powerful method to identify a useful bio-oligomer sequences from a library more quickly than current state-of-the-art technology allows. Effector molecules for use in treatment or diagnosis of disease are also provided.
Claims13
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).
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).
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).
Dependencies are inferred from the claim text.