Abstract: Transformations of taxol, baccatin III and of 10-deacetyl baccatin III provide access to novel taxol analogs and key intermediates thereto.

Abstract: Antibodies that catalyze the aldol reaction are generated by immunization with a reactive compound that covalently traps a Lysine (Lys) residue in the binding pocket of the antibody by formation of a stable vinylogous amide, i.e., a covalent antibody/hapten complex. The resultant catalytic antibodies employ a catalytic mechanism which mimics the catalytic mechanism employed by natural class I aldolase enzymes.

Abstract: C-2'-methylpyridinium acetates (MPA)-taxol and C-2'-methylpyridinium acetates (MPA)-taxotere are prodrugs having good aqueous solubility, low toxiticity and high anti-minor activity. These prodrugs are administered to patients for treating minors. Adminstration may be by injection or infusion.

Abstract: The present invention describes an encoded combinatorial chemical library comprised of a plurality of bifunctional molecules having both a chemical polymer and an identifier oligonucleotide sequence that defines the structure of the chemical polymer. Also described are the bifunctional molecules of the library, and methods of using the library to identify chemical structures within the library that bind to biologically active molecules in preselected binding interactions.

Abstract: Sialyl Lewis X mimetics incorporating fucopeptides are synthesized and shown to mimic the configuration and essential functional groups of sialyl Lewis X in space. The fucopeptides exhibit substantially the same biological activity as sialyl Lewis X in the E-selectin binding assay and can be employed for blocking neutrophil inflammatory conditions.

Abstract: Sleep may be induced by administration of fatty acid primary amides, including cis-9,10-octadecenoamide. Furthermore, sleep deprivation may be assayed by analyzing cerebrospinal fluid with respect to the presence of fatty acid primary amides, including cis-9,10-octadecenoamide. The presence of cis-9,10-octadecenoamide in cerebrospinal fluid is correlated with comparative sleep deprivation.

Abstract: Alkaline sensitive protaxol is water soluble and is hydrolyzed at physiological (alkaline) pH to render the native taxol structure and the native taxol activity. Protaxol compositions include 2'- and/or 7-O-ester derivatives of taxol and/or 2'- and/or 7-O-carbonate derivatives taxol. Protaxol has a formula as follows: ##STR1## wherein R.sup.1 and R.sup.2 are each H or a radical selected from the group consisting of --CO--(CH.sub.2).sub.m --X--(CH.sub.2).sub.n --COZ and --COO--(CH.sub.2).sub.o --Y--Ar, and wherein m, n, and o are each an integer of 1 to 3; X is O, S, NH, SO, or SO.sub.2 ; Y is S, SO or SO.sub.2 ; Ar is phenyl or substituted phenyl wherein the substituent is halo, amino, nitro or N,N-dialkylamino having 1 to 4 carbons in each of the alkyl groups; and Z is OH, OR.sup.3, SR.sup.3 or NR.sup.4 R.sup.5 wherein R.sup.3 is alkyl containing 1 to 4 carbons and R.sup.4 and R.sup.

Abstract: Sialyl Lewis.sup.x mimetic compounds are disclosed that are free of sialyl groups and glycosidically-linked fucosyl groups. These compounds exhibit about the same inhibition of selectin-medicated cellular adhesion as does sialyl Lewis.sup.x itself.

Abstract: Carbon linked glycosyl compounds are disclosed and synthesized. The synthesis employs a blocked carbohydrate donor and a blocked glycosyl acceptor. The blocked carbohydrate donor includes an acid labile phosphite leaving group attached to the anomeric carbon. The blocked glycosyl acceptor includes an unprotected carbon susceptible to electrophilic attack. The reaction is initiated by the addition of a Lewis acid so as to activate the acid labile phosphite leaving group on the carbohydrate donor. The substitution reaction may be conducted at -78.degree. C. in a solvent which favors the formation of carbon linked glycosylation products.

Abstract: Aureobacterium barkerei strain KDO-37-2 (ATCC 49977) and KDO aldolase (EC 4.1.2.23) isolated therefrom are disclosed. The KDO aldolase is further disclosed to have a broad substrate specificity with respect to its reverse reaction, i.e. the condensation of aldoses with pyruvate to form a wide range of 2-keto-3-deoxy-onic acids, including 2-keto-3-deoxy-nonulosonic acid, 2-keto-3-deoxy-octulosonic acid, 2-keto-3-deoxy-heptulosonic acid, and 2-keto-3-deoxy-hexulosonic acid. In particular, 3-deoxy-D-manno-2-octulosonic acid (D-KDO), a vital component of lipopolysaccharides found in the bacterial outer membrane may be synthesized from D-arabinose and pyruvate in 67% yield.

Abstract: Antibodies raised against the quaternary piperidinium haptens are shown to catalyze the aldol stereoselective addition of acetone to aldehydes using the primary benzylamine as a cofactor.

Abstract: Molecules having covalent catalytic activity are identified by panning synthetic and semisynthetic combinatorial libraries on solid phase suicide substrates. In an alternative mode, mechanism-based inhibitors or affinity labels may substituted for the suicide substrate. Covalent catalysts within the combinatorial library form covalent conjugates with the suicide substrate, mechanism-based inhibitor, or affinity label. Covalent conjugates are immobilized by attachment to the suicide substrate to solid phase and are easily separated from unconjugated elements of the combinatorial library by stringent washing. Combinatorial libraries employing phagemid-display are particularly preferred since such phagemids include genetic material for identifying and amplifying conjugated catalysts. Covalent catalysts obtainable by this method include, inter alia, molecules having esterolytic activity, aldol condensation activity, .beta.-lactamase activity, glycosidase activity, RNase activity, and proteolytic activity.

Abstract: A peptide linkage unit is employed for joining peptide and pseudopeptide sequences, including peptides and pseudopeptides that inhibit aspartic proteinase enzymes. The peptide linkage unit includes a phosphinate methylene ammonium linkage in place of a peptidyl carboxamide bond. If the peptide linkage unit is incorporated into a peptide sequence that would otherwise serve as an aspartic proteinase substrate and if it is positioned at a cleavage site within such peptide sequence, the phosphinate methylene ammonium linkage is resistant to cleavage and serves as an exploding transition state analog of such cleavage site. When so incorporated, the phosphinate methylene ammonium linkage can bind or interfere with the active site of aspartic proteinase enzymes and inhibit its activity. Preferred inhibitors contain a phosphinic acid methylene amine group joining the P.sub.1 and P.sub.1 ' residues and have a length of 3 to about 15 amino acid residues.

Abstract: A reaction cassette has been designed for the highly sensitive detection of the making and breaking of chemical bonds. The system may be employed as a companion device to be used in the search for antibody and other novel catalysts. The cassette also has important clinical applications in the design of diagnostic reagents. In its fully encoded format this methodology is capable of both detecting and decoding chemical events.

Abstract: Synthetic calicheamicin mimics employ alternative activation triggers and trigger cites and include tithers for conjugation to DNA targeting systems.

Abstract: Treatment of patients having multiple sclerosis with therapeutic agents containing substituted adenine derivatives such as 2-chloro-2'-deoxyadenosine is shown to markedly ameliorate the disease condition.

Abstract: Intermediates useful in preparing the aglycon or core structure of esperamicin are disclosed, as are methods of making and using the same.

Abstract: A method for esterifying C13 deoxy taxoid intermediates employs three steps, i.e., oxygenation of the C13 deoxy taxoid intermediate to produce a C13 enone taxoid intermediate; reduction of the C13 enone to produce an alcohol; followed by esterification of the C13 alcohol. Key intermediates include C13 deoxy taxoids; C13 enone substituted taxoids; and C1-C2 cyclo carbonate esters of taxoids.

Abstract: A method for inducing apoptosis in target cells employs designed enediynes which are triggered to become chemically reactive when bound to target cells. Conversely, a method for inhibiting the induction of apoptosis employs compounds which compete with the above compounds which induce apoptosis, but which are chemically unreactive with respect to the target cells.

Abstract: Catalytic antibodies are employed for catalyzing rearrangement reactions involving carbon-carbon bonds. The catalytic antibodies are generated using haptens that are transition state analogs of the such rearrangement reactions. More particularly, the haptens dispslay an electrostatic complementarity with the transition state. Since the formation of a transient positive charge in the migrating bond is a general feature of nucleophilic 1,2-shifts, it is disclosed that haptens for generating catalytic antibody directed to such reactions must incorporate such charge. Antibody catalysis of the dienone-phenol rearrangement is shown to catalyze both the hydronium ion promoted pathway and the spontaneous rearrangement pathway, indicating that the antibody stabilizes the localized positive charge of the transition state.