Prolinx Incorporated

Cepheid Corporation

Systemix, Inc.

Agilent Technologies, Inc.

Cambrex Bio Science Rockland, Inc.

Kevin P Lund

Mark L Stolowitz

Robert J Kaiser

Alexander A Gall

Steven M Torkelson

Mark L Stowolitz

Edward A Kesicki

Karin A Hughes

Clarence N Ahlem

Sergey G Lokhov

Mikhail A Podyminogin

Jean P Wiley

Ekaterina V Viazovkina

Dmitri Sergueev

Guisheng Li

Oliver Z Nanassy

Alex I Kutyavin

William Brabant

Maher N Qabar

Automated oligonucleotide synthesis-compatible sulforhodamine dye phosphoramidite compounds and labeled polynucleotides incorporating these dyes are provided.

Sulforhodamine phosphoramidite dyes

Methods and cleaning compositions for reduction of nucleic acid contamination on surfaces, in air, and in solutions using modified pectin are provided.

Nucleic acid decontamination methods

Automated oligonucleotide synthesis-compatible fluorescent dye phosphoramidite compounds, solid supports, and labeled polynucleotides incorporating the compounds are provided. The compounds allow universal incorporation of the fluorescent label into any position of the polynucleotide.

Fluorescent dyes

Disclosed are modified cytosine bases that provide enhanced base-pairing affinity for guanine bases in polynucleotide hybridization complexes. Also disclosed are polynucleotide oligomers, polynucleotide hybridization complexes that comprise such modified cytosine bases. Also disclosed are various methods of use. For example, in some embodiments, modified polynucleotide oligomers disclosed herein can be used as primers and probes for nucleic acid amplification and/or detection.

Modified cytosine polynucleotide oligomers and methods

Disclosed are modified thymine bases that provide enhanced base-pairing affinity for adenine or 2,6-diaminopurine bases in polynucleotide hybridization complexes. Also disclosed are polynucleotide oligomers, polynucleotide hybridization complexes that comprise such modified thymine bases. Also disclosed are various methods of use. For example, in some embodiments, modified polynucleotide oligomers disclosed herein can be used as primers and probes for nucleic acid amplification and/or detection.

Modified thymine polynucleotide oligomers and methods

The present invention provides a sensor surface comprising: a substrate coated with a free electron metal; and a matrix layer disposed on the free electron metal, wherein the matrix layer comprises an organic compound having a boronic acid complexing moiety. The matrix is preferably a self-assembled monolayer (SAM), a mixed self-assembled monolayer (mSAM), or combinations thereof.

Sensor surfaces for detecting analytes

The present invention provides a method for detecting an analyte, comprising providing a sensor comprising a substrate coated with a free electron metal, a matrix layer disposed on the free electron metal, the matrix layer comprising an organic compound, wherein the organic compound has a boronic acid complexing moiety and, a boronic acid moiety complexed to the boronic acid complexing moiety; and contacting the sensor with the analyte to elicit a response; and measuring the response thereby detecting the analyte.

Sensor surfaces for detecting analytes and methods of use

A reagent having the general formula of General Formula I:wherein group R is an electrophilic or a nucleophilic moiety suitable for reaction of the reagent with a biologically active species; group Ris one of H and OH moieties; group Ris one of an alkyl and a methylene bearing an electronegative substituent; group Z is one of (CH)and CHO(CHCHO), and n is an integer of from 1 to 5, and nis an integer of from 1 to 4; and each of group Zand Zare (CH)CONH(CH)CONH(CH). Also, a reagent having the general formula of General Formula II:group Ris one of H and OH moieties; group Z is one of (CH)and CHO(CHCHO), and n is an integer of from 1 to 5, and nis an integer of from 1 to 4; each of group Zand group Zinclude one of (CH)CONH(CH)CONH(CH); and (CH)CONH(CH); and group R is an electrophilic or a nucleophilic moiety suitable for reaction of the reagent with the biologically active species.

Bifunctional boronic compound complexing reagents and complexes

Phenyldiboronic acid reagents and complexes

Reagents suitable for the modification of a bioactive species for the purpose of incorporating a bifunctional boronic compound complexing moiety for subsequent conjugation to a different (or the same) bioactive species having pendant phenylboronic acid moieties of General Formula 1, ##STR1## wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the putative bifunctional boronic compound complexing reagent with a bioactive species, wherein group R.sub.2 is selected from one of H and OH moieties, and wherein group R.sub.3 is selected from one of an alkyl and a methylene bearing an electronegative substituent. Group Z is a spacer selected from (CH.sub.2).sub.n and CH.sub.2 O(CH.sub.2 CH.sub.2 O).sub.n.sbsb.2, wherein n is an integer of from 1 to 5, and wherein n.sub.2 is an integer of from 1 to 4. Each of group Z.sub.2 and Z.sub.3 is a spacer selected from CH.sub.2 Ar, CH.sub.2 CONHCH.sub.2 Ar, CH.sub.2 CONH(CH.sub.2).sub.n.sbsb.3 CO--NHCH.sub.2 Ar, and (CH.sub.2).sub.n.sbsb.4 NHCO(CH.sub.2).sub.n.sbsb.5 CONHCH.sub.2 Ar, wherein the group Ar represents the aromatic ring in the reagent of General Formula I to which the spacer Z.sub.2 or Z.sub.3 is appended, wherein n.sub.3 is an integer of from 1 to 5, wherein n.sub.4 is an integer selected from one of 2 and 3, and wherein n.sub.5 is an integer of from 1 to 4. Reaction of a reagent of General Formula I with a bioactive species affords a conjugate having pendant putative bifunctional boronic compound complexing moieties. (one or more) The conjugate may be further reacted with hydroxylamine (NH.sub.2 OH) by amidation of the benzoic acid ester moiety to afford a class of bifunctional boronic compound complexing conjugate, e.g., conjugate with one or more pendant bifunctional boronic compound complexing moieties.

Reagents suitable for the modification of a bioactive species for the purpose of incorporating one or more phenyldiboronic acid (PDBA) moieties for subsequent conjugation to a different (or the same) bioactive species having one or more pendant boronic compound complexing moieties of the general formula of General Formula I, ##STR1## wherein group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the PDBA reagent with a bioactive species. Group Z is a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length. Group Q is a linkage that includes one of amide, ether and thioether moieties. Group R is preferably selected from, but not limited to, one of acrylamide, bromo, bromoacetamide, chloro, chloroacetamide, dithiopyridyl, hydrazide, N-hydroxysuccinimidyl ester, N-hydroxysulfo-succinimidyl ester, imidate ester, imidazolide, iodo, iodoacetamide, maleimide, amino and thiol moieties. Group Z is preferably an unbranched alkyl chain of the general formula (CH.sub.2)n, wherein n=1 to 6. Group Q is preferably selected from one of NHCO, CONH, NHCOCH.sub.2, CONHCH.sub.2, O, OCH.sub.2, S and SCH.sub.2 moieties.

Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula CIII, General Formula CIV, and General Formula CVI. In one embodiment, the reagents of General Formula CIII may be used to produce, after condensation with a bioactive species (BAS), the reagent of General Formula CIV. The reagent of General Formula CIV may be used to form a complex with a boron compound, such as a complex shown in General Formula CVI. ##STR1##

Boron compound completing reagents, intermediate reagents of those reagents and methods of synthesizing these reagents. These reagents, including those shown as General Formula CII may be used, after further reactions described herein, to complex with boronic compounds, such as phenylboronic acid or derivatives thereof. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one of intermediate amide and disulfide moieties, and a polyethylene glycol chain of from 3 to 12 carbon equivalents in length; group R.sub.2 is one of an alkyl and a methylene with an electronegative moiety; and BAS is a biologically active species.

Boronic compound complexing reagents and highly stable complexes

Boron compound complexing reagents, boron compound complexes, and methods of synthesizing these reagents and complexes are disclosed. These reagents and complexes include those shown in General Formula CIV, and General Formula CVI. In one embodiment, the reagent of General Formula CIV may be used to form a complex with a boron compound, such as a complex shown in General Formula CVI. ##STR1## In one embodiment, group Z comprises a spacer selected from a saturated or unsaturated chain of up to about 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one of intermediate amide and disulfide moieties, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; group R.sub.3 is selected from one of an H, an alkyl, and a methylene or ethylene moiety with an electronegative substituent; and BAS and BAS* are biologically active species.

Growing community of inventors

Lynnwood, WA, United States of America

Kevin P Lund