Abstract: Proteins of moderate size having native peptide backbones are produced by a method of native chemical ligation. Native chemical ligation employs a chemoselective reaction of two unprotected peptide segments to produce a transient thioester-linked intermediate. The transient thioester-linked intermediate then spontaneously undergoes a rearrangement to provide the full length ligation product having a native peptide bond at the ligation site. Full length ligation products are chemically identical to proteins produced by cell free synthesis. Full length ligation products may be refolded and/or oxidized, as allowed, to form native disulfide-containing protein molecules. The technique of native chemical ligation is employable for chemically synthesizing full length proteins.

Abstract: Fluorescent dyes possess reactive linkers for conjugating to nucleic acids, carbohydrates and peptides. The conjugates fluoresce in the visible and UV spectrum and have an excellent solvochromatic response as compared to other fluorescence or chromatic labels. The conjugates are stable but also have medium sensitive. The fluorescent dyes have little triplet state formation and are not photoreactive, making them an excellent substance for biological investigations. Uses for the dyes include protein labeling, DNA labeling, single molecule spectroscopy and fluorescence. A synthesis of the dyes is disclosed. Methods of use include the detection of carbohydrate-protein interactions.

Abstract: The invention relates to the combination of hydroxyamines with nucleic acid binding motifs to generate molecules and libraries of molecules targeting specific nucleic acid sequences. In particular, a series of libraries are constructed which contain hydroxyamine functionalities that are attached to various template backbones which display varying degrees of molecular recognition to phosphodiesters and varying degrees of sequence specific recognition to nucleic acids.

Abstract: Bioactive fucopeptides and libraries of fucopeptides having advanced activities against P-selectin as sialyl Lewis X mimetics with IC.sub.50 values in the low mM range are synthesized by solid phase synthesis using para-acyloxymethylenzlidene acetal (p-AMBA) as an anchoring group. A rapid parallel synthesis is employed which proceeds with a bi-directional functionalization of glycosylated amino acid derivatives.

Abstract: Inhibitors of oleamide hydrolase, responsible for the hydrolysis of an endogenous sleep-inducing lipid (1, cis-9-octadecenamide) were designed and synthesized. The most potent inhibitors possess an electrophilic carbonyl group capable of reversibly forming a (thio) hemiacetal or (thio) hemiketal to mimic the transition state of a serine or cysteine protease catalyzed reaction. In particular, the tight binding .alpha.-keto ethyl ester 8 (1.4 nM) and the trifluoromethyl ketone inhibitor 12 (1.2 nM) were found to have exceptional inhibitory activity. In addition to the inhibitory activity, some of the inhibitors displayed agonist activity which resulted in the induction of sleep in laboratory animals.

Abstract: 2-Ketoaldonic acid is synthesized by aldolase condensation reaction involving pyruvate and an aldose acceptor in the presence of excess pyruvate. After the reaction is substantially complete, the excess pyruvate is removed from the reaction mixture by treatment with pyruvate decarboxylase.

Abstract: Analogs of antitumor antibiotics CC-1065 and the duocarmycins are synthesized which possess systematic and extensive modifications in the DNA binding subunits attached to a 1,2,9,9a-tetra-hydro-cyclo-propa[c]benz[e]indol-4-one (CBI) alkylation subunit. The analogs have potent cytotoxic activity and are efficacious antitumor compounds.

Abstract: Anthraquinone chiral ligands (AQN) are used in asymmetric aminohydroxylation addition reactions of cinnamate based olefins for synthesizing aryl serines. The anthraquinones impart a reverse regioselectivity as compared to the commonly employed phalazine chiral ligands (PHAL). Carbamates are employed as the oxidant nitrogen source. The yields and enantiomeric efficiencies are Excellent. .beta.-Hydroxyamines are obtained by deprotecting the corresponding .beta.-hydroxycarbamate.

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: D-enzyme compositions are described comprising an amino acid residue sequence that defines an polypeptide able to catalyze an enzymatic reaction. The D-enzyme has an amino acid residue sequence consisting essentially of D-amino acids.

Abstract: Onium salts of taxo-diterpenoid-C.sup.n, 2-0-aza-arenes are employed as water soluble prodrugs. For example, taxol-2'-methylpyridiniumtosylate (MPT) is characterized by an elevated aqueous solubility, rapid activation by serum protein, good stability in most other aqueous solutions, formation of a protein:taxol intermediate and good retension within the circulatory system. The toxicity of the activated form is comparable or greater than underivatized taxol. Furthermore, taxol-2'-MPT can be synthesized by a simple one step reaction between taxol and 2-fluoro-1-MPT. The invention is applicable to taxol and taxol mimetics having hydroxyls that are reactive with onium salts of 2-halogenated-aza-arenes. For example, taxol, C-2 substituted analogs of taxol, and Taxotere each have reactive hydroxyls at the 2' and 7 positions. The invention is also applicable to a wide array of 2-halogenated-aza-arenes.

Abstract: Tert-alkyl sulfonamides chloramine salts are used as nitrogen sources in the catalytic aminohydroxylation and/or aziridination of olefins. The tert-alkyl sulfonamides chloramine salts are close to Chloramine T with respect to their reactivity as nitrogen sources with olefins. However, unlike the tosyl sulfonyl amine group of Chloramine T, the resulting t-alkyl sulfonylamino functionalities can be easily converted to an unprotected amine under mild acidic conditions making the method a simple and cost efficient approach for producing unsubstituted hydroxy amine and/or aziridine products.

Abstract: D- and L-.alpha.-amino acids and D- and L-.alpha.-amino aldehydes are synthesized from olefin substrates in two steps. The first step is a catalyzed asymmetric aminohydroxylation addition reaction to the olefin substrate. The addition reaction is catalyzed by osmium and is co-catalyzed by chiral ligands. The chiral ligands, in addition to being co-catalysts with the osmium, also serve to direct the addition reaction regioselectively and enantioselectively. Divalent ligands are preferred over monovalent ligands because of their enhance regio- and enantio-selectivity. As an oxidant nitrogen source for the addition reaction, either a carbamate or sulfonamide may be employed. If carbamate is employed as an oxidant nitrogen source, the resultant .beta.-hydroxycarbamate is deprotected to yield the corresponding .beta.-hydroxyamine. If sulfonamide is employed as an oxidant nitrogen source, the resultant .beta.-hydroxysulfonamide is deprotected to yield the corresponding .beta.-hydroxyamine. The resultant .beta.

Abstract: MCBI (7-methoxy-1,2,9a-tetra-hydrocyclopropa[c]benz[e]indol-4-one) is employable as a DNA alkylating agent and can be incorporated into analogs of CC-1065 and the duocarmycins for constructing regioselective DNA alkylating agents.

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: Racemic amines are enzymically converted by enantioselective carbamation to produce to chiral carbamates. Simple homocarbonates employed as substrates. The chiral carbamates may then be deprotected to yield the original amine in a chiral form. Alternatively, the chiral carbamates may be reduced so as to produce methylated chiral amines.

Abstract: Sarcodictyin A and B, eleutherobin, and bioactive analogs thereof synthesized using solid phase and solution phase chemistries. The synthetic method employs an attachment of common precursors, e.g., compounds 1880 or 200, on a solid support for generating conjugates 230 and 240, followed by standard chemical manipulations. A combinatorial library of sarcodictyins and eletherobin analogs was constructed with modified C-8 ester, C-15 ester and C-4 ketal functionalities and was screened for activity with respect to tubulin polymerization and cytotoxic activity against tumor cells, including Taxol-resistant lines. Compounds 600, 610, 630, 660-700, 730, 760, 850, and 920 were identified to be of equal or superior biological activities as compared to their corresponding natural product.

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 inflamatory conditions.

Abstract: Fluorescent dyes possess reactive linkers for conjugating to nucleic acids, carbohydrates and peptides. The conjugates fluoresce in the visible and UV spectrum and have an excellant solvochromatic response as compared to other fluorescence or chromatic labels. The conjugates are stable but also have medium sensitive. The fluorescent dyes have little triplet state formation and are not photoreactive, making them an excellent substance for biological investigations. Uses for the dyes include protein labelling, DNA labelling, single molecule spectroscopy and fluorescence. A synthesis of the dyes is disclosed. Methods of use include the detection of carbohydrate-protein interactions.

Abstract: Rhenium-catalyzed epoxidation of olefinic substrates is accelerated by the use of acclerants having a nitrogenous aromatic heterocyclic structure. Use of the accelerants also enables the use of aqueous hydrogen peroxide as an oxidant. To achieve optimum acceleration, the accelerant should have a concentration within a range from 2.0 mole percent to 100 mole percent of the acclerant with respect to 1 mole of the olefinic substrate. Use of the accelerant also results in an increased yield with respect to the conversion of the olefinic substrate to epoxide product.