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US 2004/0110730 A1Published application
Hydrazine-based and carbonyl-based bifunctional crosslinking reagents
AssigneeSolulink Biosciences, Inc.
InventorDavid A. Schwartz
Life of this patent
Estimating the term…
Abstract
Reagents and methods are provided for crosslinking and immobilizing biomolecules, drugs and synthetic polymers. The reagents possess (i) a thiol or amino reactive group; and (ii) a hydrazino or oxyamino moiety. Conjugates and immobilized biomolecules are also provided.
Claims53
A compound of formula I:
- B—R—A—NHNH2.HX I
- or a derivative thereof, wherein:
- A is —NH(C═O)—, —NH(C═S)—, —NHNH(C═O)—, —NHNH(C═S)—, or a direct bond to R;
- B is an amino or thiol reactive moiety;
- R is an aliphatic divalent group having any combination of the following groups, which are combined in any order:
- cycloalkylene, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylen, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group sel cted from hydrogen, alkyl, alk nyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- and
- X is a negative counterion.
28 more elements
A compound of formula II:
- B—R—A—NHN═C(R1R2) II
- or a derivative thereof, wherein:
- A is NH(C═O)—, NH(C═S)—, NHNH(C═O)—, or NHNH(C═S)— or a direct bond to R;
- B is an amino or thiol reactive moiety;
- R is an aliphatic divalent group having any combination of the following groups, which are combined in any order:
- cycloalkylene, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C, O—, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitr , SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, h t roaryl, h t roaralkyl, heteroaralkenyl, het roaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, het roaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- R1 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- and
- R2 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms.
29 more elements
A compound of formula III:
- B—R—(C═O)—NHNH2.HX III
- or a derivative thereof, wherein:
- B is an amino reactive moiety;
- R is an aliphatic divalent group having any combination of the following groups, which are combined in any order:
- cycloalkylene, C(R10)2, —C(R10)═C(R10)—;
- >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combin d in any order:
- a direct link, arylene, het roarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C, O, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13) and C(L);
- wh re a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independ ntly selected from among hydrogen, halo, ps udohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- and
- X is a negative counterion.
28 more elements
A compound that has one of formulae VII or VIII:
- B—R—ONH2.HX VII;
- orB—R—ON═C(R1R2) VIII
- or a derivative thereof, wherein:
- R is a divalent group having any combination of the following groups, which are combined in any order:
- arylene, heteroarylene, cycloalkylene, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R4;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alk nyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, h teroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalk nyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, h teroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R1, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- B is an amino or thiol reactive moiety;
- R1 is H or a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- R2 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- and
- X is a negative counterion.
30 more elements
A compound that has any of formulae XI:
- 17
- or a derivative thereof, wherein:
- R3 is a straight chain, branched or cyclic alkyl group of 1-10 carbons;
- R1 is H or a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- R2 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- X is a negative counterion;
- R is a divalent group having any combination of the following groups, which are combined in any order:
- arylene, heteroarylene, cycloalkylene, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13) —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O or NR15;
- R14 and R15 are each independently s I cted from the group among hydrog n, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- and
- A is a direct link, NH(C═O), NH(C═S), NHNH(C═O), or NHNH(C═S).
30 more elements
A compound that has one of formulae XII:
- 19
- or a derivative thereof, wherein:
- R3 is a straight chain, branched or cyclic alkyl group of 1-10 carbons;
- R1 is H or a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- R2 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- X is a n gative counterion;
- and
- R is a divalent group having any combination of the following groups, which are combined in any order:
- arylene, heteroarylen, cycloalkyl ne, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G1)a, P(J)b(R15) P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O, or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or mor substitu nts each independently selected from Z, wh r in Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R3, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino.
29 more elements
A compound that has any of formulae XIII:
- R3 S—R—A—NHNH2.HX,R30S—R—A—NHN═CR1R2,(S—R—A—NHNH2.HX)2, or(S—R—A—NHN═CR1R2)2;
- or a derivative thereof, wherein
- R1 is H or a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- R2 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- X is a negative counterion;
- and
- R is a divalent group having any combination of the following groups, which are combined in any order:
- arylene, heteroarylene, cycloalkylene, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O, or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O, or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, he teroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently selected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- A is a direct link, C═O, C═S, NH(C═O), NH(C═S), NHNH(C═O), or NHNH(C═S);
- and
- R30 is hydrogen or a thiol protecting group.
31 more elements
A compound that has one of formulae XII:
- R30S—R—ONH2.HX,R30S—R—ON═CR1R2,(S—R—ONH2.HX)2, or(S—R—ON═CR1R2)2;
- or a derivative thereof, wher in
- R1 is H or a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- R2 is a saturated straight chain of 3 to 20 carbon atoms, a chain of 2 to 2000 ethyleneoxide moieties, or a saturated or unsaturated carbocyclic moiety of 3 to 20 carbon atoms;
- X is a negative counterion;
- and
- R is a divalent group having any combination of the following groups, which are combined in any order:
- arylene, heteroarylene, cycloalkylene, C(R10)2, —C(R10)═C(R10)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G)a, P(J)b(R10), P(J)b(LR10), N(R10), >N+(R12)(R13) and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G is O or NR10;
- J is S or O;
- and L is S, O, or NR10;
- each R10 is a monovalent group independently selected from hydrogen and M1-R14;
- each M1 is a divalent group independently having any combination of the following groups, which groups are combined in any order:
- a direct link, arylene, heteroarylene, cycloalkylene, C(R15)2, —C(R15)═C(R15)—, >C═C(R12)(R13), >C(R12)(R13), —C≡C—, O, S(G1)a, P(J)b(R15), P(J)b(LR15), N(R15), N(COR15), >N+(R12)(R13), and C(L);
- where a is 0, 1 or 2;
- b is 0, 1, 2 or 3;
- G1 is O or NR15;
- J is S or O;
- and L is S, O, or NR15;
- R14 and R15 are each independently selected from the group among hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR16R17R18, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- R19 and R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;
- R12 and R13 are selected from (i) or (ii) as follows:
- (i) R12 and R13 are independently s lected from among hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;
- or (ii) R12 and R13 together form alkylene, alkenylene or cycloalkylene;
- R16, R17 and R18 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR19R20;
- and
- R11, R12, R13, R14, R15, R16, R17, R18, R19 and R20 can be substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR30, NR30R31, COOR30, COR30, CONR30R31, OC(O)NR30R31, N(R30)C(O)R31, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;
- h is 0, 1 or 2;
- and R30 and R31 are each independently selected from among hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino;
- and
- R30 is hydrogen or a thiol protecting group.
30 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula IVa:
- 21
- or a derivative thereof, wherein:
- A is NH(C═O), NH(C═S), NH(C═NH), NHNH(C═O), NHNH(C═S), NHNH(C═NH) or a direct bond;
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- and
- X is a negative counter ion, oxygen, sulfur or —NH;
- and
- (ii) applying the conjugate to a surface wherein the surface has at least one carbonyl moiety for a time and under conditions such that the hydrazine moiety of the conjugate reacts with the carbonyl moiety of the surface forming a hydrazone bond to the surface.
8 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula Va:
- 22
- or a derivative thereof, wherein:
- A is NH(C═O), NH(C═S), NH(C═NH), NHNH(C═O), NHNH(C═S), NHNH(C═NH) or a direct bond;
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- R1 is hydrogen or a saturated straight chain of 1 to 12 carbon atoms;
- and
- R2 is hydrogen or a saturated straight chain of 1 to 12 carbon atoms;
- and
- (ii) applying the conjugate to a surface wherein the surface has at least one amino or one thiol reactive moiety for a time and under conditions such that the conjugate reacts with the amino or thiol reactive moiety of the surface forming a bond to the surface.
9 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of the formula VIa:
- 23
- or a derivative thereof, wherein:
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- and
- X is a negative counter ion, oxygen, sulfur or —NH;
- and
- (ii) applying the conjugate to a surface wherein the surface has at least one carbonyl moiety for a time and under conditions such that the hydrazine moiety of the conjugate reacts with the carbonyl moiety of the surface forming a hydrazone bond to the surface.
7 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula IVa:
- 24
- or a derivative thereof, wherein:
- A is NH(C═O), NH(C═S), NH(C═NH), NHNH(C═O), NHNH(C═S), NHNH(C═NH) or a direct bond;
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- and
- X is a negative counter ion, oxygen, sulfur or —NH;
- and
- (ii) applying the conjugate to a surface wherein the surface has at least one amino or one thiol reactive moiety for a time and under conditions such that the conjugate reacts with the amino or thiol reactive moiety of the surface forming a bond to the surface.
8 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula Va:
- 25
- or a derivative thereof, wherein:
- A is NH(C═O), NH(C═S), NH(C═NH), NHNH(C═O), NHNH(C═S), NHNH(C═NH) or a direct bond;
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrog n atom;
- E is a carbon or nitrogen atom;
- R1 is hydrogen or a saturated straight chain of 1 to 12 carbon atoms;
- and
- R2 is hydrogen or a saturated straight chain of 1 to 12 carbon atoms;
- and
- (ii) applying the conjugate to a surface wherein the surface has at least one amino or one thiol reactive moiety for a time and under conditions such that the conjugate reacts with the amino or thiol reactive moiety of the surface forming a bond to the surface.
9 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula VIa:
- 26
- or a derivative thereof, wherein:
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- and
- X is a negative counter ion, oxygen, sulfur or —NH;
- and
- (ii) applying the conjugate to a surface wherein the surface has at least one amino or one thiol reactive moiety for a time and under conditions such that the conjugate reacts with the amino or thiol reactive moiety of the surface forming a bond to the surface.
7 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula IVa:
- 27
- or a derivative thereof, wherein:
- A is NH(C═O), NH(C═S), NH(C═NH), NHNH(C═O), NHNH(C═S), NHNH(C═NH) or a direct bond;
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- and
- X is a negative counter ion, oxygen, sulfur or —NH;
- and
- (ii) mixing the conjugate to a natural or synthetic biological molecule, wherein the molecule has at least one carbonyl moiety, for a time and under conditions such that the hydrazine moiety of the conjugate reacts with the carbonyl moiety of the molecule forming a hydrazone bond to the molecule.
8 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula Va:
- 28
- or a derivative thereof, wherein:
- A is NH(C═O), NH(C═S), NH(C═NH), NHNH(C═O), NHNH(C═S), NHNH(C═NH) or a direct bond;
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- R1 is hydrogen or a saturated straight chain of 1 to 12 carbon atoms;
- and
- R2 is hydrogen or a saturated straight chain of 1 to 12 carbon atoms;
- and
- (ii) mixing the conjugate with a natural or synthetic biological molecule, wherein the molecule has at least one carbonyl moiety, for a time and under conditions such that the hydrazine moiety of the conjugate reacts with the carbonyl moiety of the molecule forming a hydrazone bond to the molecule.
9 more elements
A method of crosslinking a natural or synthetic biological molecule, comprising:
- (i) preparing a conjugate of formula VIa:
- 29
- or a derivative thereof, wherein:
- B is a natural or synthetic biological molecule;
- D is a carbon or nitrogen atom;
- E is a carbon or nitrogen atom;
- and
- X is a negative counter ion, oxygen, sulfur or —NH;
- and
- (ii) mixing the conjugate with a natural or synthetic biological molecule, wherein the molecule has at least one carbonyl moiety for a time and under conditions such that the hydrazine moiety of the conjugate reacts with the carbonyl moiety of the molecule forming a hydrazone bond to the molecule.
7 more elements
Dependencies are inferred from the claim text.