Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Synthesis of peptides
Reexamination Certificate
1999-12-17
2003-05-20
Zitomer, Stephanie (Department: 1634)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Synthesis of peptides
C435S006120, C435S007100, C530S300000, C530S335000, C530S336000, C530S337000, C530S350000, C530S387100, C536S024300, C536S025300, C536S025310
Reexamination Certificate
active
06566495
ABSTRACT:
COPYRIGHT NOTICE
A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.
BACKGROUND OF THE INVENTION
The present invention relates to the field of polymer synthesis. More specifically, the invention provides a reactor system, a masking strategy, photoremovable protective groups, data collection and processing techniques, and applications for light directed synthesis of diverse polymer sequences on substrates.
SUMMARY OF THE INVENTION
Methods, apparatus, and compositions for synthesis and use of techniques for diverse polymer sequences on a substrate are disclosed, as well as applications thereof.
According to one aspect of the invention, an improved reactor system for synthesis of diverse polymer sequences on a substrate is provided. According to this embodiment the invention provides for a reactor for contacting reaction fluids to a substrate; a system for delivering selected reaction fluids to the reactor; a translation stage for moving a mask or substrate from at least a first relative location relative to a second relative location; a light for illuminating the substrate through a mask at selected times; and an appropriately programmed digital computer for selectively directing a flow of fluids from the reactor system, selectively activating the translation stage, and selectively illuminating the substrate so as to form a plurality of diverse polymer sequences on the substrate at predetermined locations.
The invention also provides a technique for selection of linker molecules in VLSIPS. According to this aspect of the invention, the invention provides a method of screening a plurality of linker polymers for use in binding affinity studies. The invention includes the steps of forming a plurality of linker polymers on a substrate in selected regions, the linker polymers formed by the steps of recursively: on a surface of a substrate, irradiating a portion of the selected regions to remove a protective group, and contacting the surface with a monomer; contacting the plurality of linker polymers with a ligand; and contacting the ligand with a labeled receptor.
According to another aspect of the invention, improved photoremovable protective groups are provided. According to this aspect of the invention a compound having the formula:
wherein n=0 or 1; Y is selected from the group consisting of an oxygen of the carboxyl group of a natural or unnatural amino acid, an amino group of a natural or unnatural amino acid, or the C-5′ oxygen group of a natural or unnatural deoxyribonucleic or ribonucleic acid; R
1
and R
2
independently are a hydrogen atom, a lower alkyl, aryl, benzyl, halogen, hydroxyl, alkoxyl, thiol, thioether, amino, nitro, carboxyl, formate, formamido, sulfido, or phosphido group; and R
3
is a alkoxy, alkyl, aryl, hydrogen, or alkenyl group is provided.
The invention also provides improved masking techniques for VLSIPS. According to one aspect of the masking technique, the invention provides an ordered method for forming a plurality of polymer sequences by sequential addition of reagents comprising the step of serially protecting and deprotecting portions of the plurality of polymer sequences for addition of other portions of the polymer sequences using a binary synthesis strategy.
Improved data collection equipment and techniques are also provided. According to one embodiment, the instrumentation provides a system for determining affinity of a receptor to a ligand comprising: means for applying light to a surface of a substrate, the substrate comprising a plurality of ligands at predetermined locations, the means for applying directing light providing simultaneous illumination at a plurality of the predetermined locations; and an array of detectors for detecting light fluoresced at the plurality of predetermined locations. The invention further provides for improved data analysis techniques including the steps of exposing fluorescently labelled receptors to a substrate, the substrate comprising a plurality of ligands in regions at known locations; at a plurality of data collection points within each of the regions, determining an amount of light fluoresced from the data collection points; removing the data collection points deviating from a predetermined statistical distribution; and determining a relative binding affinity of the receptor to remaining data collection points.
Protected amino acid N-carboxy anhydrides for use in polymer synthesis are also disclosed. According to this aspect of the invention provides a compound having the formula:
where R is a side chain of a natural or unnatural amino acid and X is a photoremovable protecting group.
A further understanding of the nature and advantages of the inventions herein may be realized by reference to the remaining portions of the specification and the attached drawings.
REFERENCES:
patent: 3730844 (1973-05-01), Gilham et al.
patent: 3849137 (1974-11-01), Barzynski et al.
patent: 3862056 (1975-01-01), Hartman
patent: 3939350 (1976-02-01), Kronick et al.
patent: 4072576 (1978-02-01), Arwin et al.
patent: 4121222 (1978-10-01), Diebold et al.
patent: 4180739 (1979-12-01), Abu-Shumays
patent: 4216245 (1980-08-01), Johnson
patent: 4238757 (1980-12-01), Schenck
patent: 4269933 (1981-05-01), Pazos
patent: 4314821 (1982-02-01), Rice
patent: 4327073 (1982-04-01), Huang
patent: 4339528 (1982-07-01), Goldman
patent: 4342905 (1982-08-01), Fujii et al.
patent: 4373071 (1983-02-01), Itakura
patent: 4395486 (1983-07-01), Wilson et al.
patent: 4405771 (1983-09-01), Jagur
patent: 4444878 (1984-04-01), Paulus
patent: 4444892 (1984-04-01), Malmros
patent: 4448534 (1984-05-01), Wertz et al.
patent: 4458066 (1984-07-01), Caruthers et al.
patent: 4477556 (1984-10-01), Dueber et al.
patent: 4478967 (1984-10-01), Eian et al.
patent: 4483920 (1984-11-01), Gillespie et al.
patent: 4500707 (1985-02-01), Caruthers et al.
patent: 4500919 (1985-02-01), Schreiber
patent: 4516833 (1985-05-01), Fusek
patent: 4517338 (1985-05-01), Urdea et al.
patent: 4533682 (1985-08-01), Tortorello et al.
patent: 4537861 (1985-08-01), Elings et al.
patent: 4542102 (1985-09-01), Dattagupta et al.
patent: 4555490 (1985-11-01), Merril
patent: 4556643 (1985-12-01), Paau et al.
patent: 4562157 (1985-12-01), Lowe et al.
patent: 4563419 (1986-01-01), Ranki et al.
patent: 4569967 (1986-02-01), Kornreich et al.
patent: 4580895 (1986-04-01), Patel
patent: 4584277 (1986-04-01), Ullman
patent: 4588682 (1986-05-01), Groet et al.
patent: 4591570 (1986-05-01), Chang
patent: 4598049 (1986-07-01), Zelinka et al.
patent: 4613566 (1986-09-01), Potter
patent: 4624915 (1986-11-01), Schindler et al.
patent: 4626684 (1986-12-01), Landa
patent: 4631211 (1986-12-01), Houghten
patent: 4637861 (1987-01-01), Krull et al.
patent: 4656127 (1987-04-01), Mundy
patent: 4670380 (1987-06-01), Dattagupta
patent: 4677054 (1987-06-01), White et al.
patent: 4681859 (1987-07-01), Kramer
patent: 4683195 (1987-07-01), Mullis et al.
patent: 4683202 (1987-07-01), Mullis
patent: 4689405 (1987-08-01), Frank et al.
patent: 4704353 (1987-11-01), Humphries et al.
patent: 4711955 (1987-12-01), Ward et al.
patent: 4713326 (1987-12-01), Dattagupta et al.
patent: 4713347 (1987-12-01), Mitchell et al.
patent: 4715413 (1987-12-01), Backlund et al.
patent: 4715929 (1987-12-01), Ogawa
patent: 4716106 (1987-12-01), Chiswell
patent: 4719179 (1988-01-01), Barany
patent: 4719615 (1988-01-01), Feyrer et al.
patent: 4722906 (1988-02-01), Guire
patent: 4728502 (1988-03-01), Hamill
patent: 4728591 (1988-03-01), Clark et al.
patent: 4731325 (1988-03-01), Palva et al.
patent: 4737344 (1988-04-01), Koizumi et al.
patent: 4755458 (1988-07-01), Rabbani et al.
patent: 4758727 (1988-07-01), Tomei et al.
patent: 4762881 (1988-08-01), Kauer
patent: 4766062 (1988-08-01), Diamond et al.
patent: 4767700 (1988-
Fodor Stephen P. A.
Pirrung Michael C.
Read J. Leighton
Stryer Lubert
Affymetrix Inc.
Liebeschuetz, Esq. Joe
McGarrigle, Esq. Philip
Treannie, Esq. Lisa M.
Zitomer Stephanie
LandOfFree
Very large scale immobilized polymer synthesis does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Very large scale immobilized polymer synthesis, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Very large scale immobilized polymer synthesis will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3001073