Prolinx Incorporated

Cambrex Bio Science Rockland, Inc.

Clarence N Ahlem

Mark L Stolowitz

Kevin P Lund

Robert J Kaiser

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

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.

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La Jolla, CA, United States of America

Clarence N Ahlem