ÐNovel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit star®sh oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in puri®ed extracts. Structure±activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethan...

ÐThe aromatic diacid residue 4,6-dibenzofuranbispropionic acid (1) was designed to nucleate a parallel b-sheet-like structure in small peptides in aqueous solution via a hydrogen-bonded hydrophobic cluster. Even though a 14-membered ring hydrogen bond necessary for parallel b-sheet formation is favored in simple amides composed of 1, this hydrogen bonding interaction does not appear to be suci...

ÐThe theory of absolute reaction rates suggests that enzymes, like other catalysts, can enhance the rate of a reaction only to the extent that they bind the altered substrate in the transition state (S{) more tightly than they bind the substrate in the ground state (S). ES dissociation constants commonly fall in the physiological range, but recent kinetic studies indicate that formal ES{ dissoc...

ÐN-Benzoyloxy-2-thiopyridone (12) was shown to induce single-strand nicks in duplex DNA upon irradiation with visible light (l&350 nm). This ®nding led to the design of a series of compounds, in which an acridinyl nucleus was covalently linked to the N-benzoyloxy-2-thiopyridone unit. These conjugates (15, 16, 17 and 18) were synthesized and evaluated as novel DNA photocleaving reagents. Optimal...

ÐThe proteolytic release, or shedding, of a cell surface protein can serve a regulatory role; the process liberates a soluble form of the protein into circulation while downregulating its cell surface concentration. The characteristics that render a protein susceptible to proteolytic cleavage are not known. We hypothesized that the clustering of a protein at the cell surface might target it for...

ÐUtilization of 17-keto-androstanes as starting materials for the synthesis of aor b-oriented steroidal 20!16-g-carbolactones has been explored following two di€erent strategies. A highly ecient, stereospeci®c protocol has been developed for the boriented cis-g-lactone. A di€erent approach, involving prior attachment of a 3-carbon side chain on C-17 of a 17-oxo-16b-acetoxyandrostane led to the...

Akaraet--The structural and functional domains of Escherichia coil carbamoyl phosphate synthetase (CPS) have been identified by limited proteolysis. Incubation of CPS with several proteases, including trypsin, chymotrypsin, subtilisin and endoproteinase Asp-N, under native conditions, causes a time-dependent loss of enzymatic activity and the generation of a common fragmentation pattern. Amino-...

-Philanthotoxins are noncompetitive inhibitors of the nicotinic acetylcholine receptor and the various glutamate r<.~ceptors. Analogues carrying photoaffinity labels, fluorine atoms for solid-state NMR studies of ligand/receptor interaction, and large head groups such as porphyrins and planar bulky aromatic rings (BIG analogues) for clarifying mode of entry and orientation of analogues in recep...

ÐAllatostatins are 6±18 amino acid peptides synthezed by insects to control production of juvenile hormones, which in turn regulate functions including metamorphosis and egg production. Four insect allatostatin neuropeptide analogues incorporating turn-promoting pseudopeptide moieties in the region responsible for biological activity were prepared by solid phase peptide synthetic methods. Bioas...

-Sesquiterpenoids, 7-hydroxy-3,4-dihydrocadalin and 7-hydroxycadalin, and flavonoids, quercetin, kaempferol and their glycosides, isolated from Heterotheca inuloides (Asteraceae), a Mexican medicinal plant known as "arnica", were evaluated as antioxidants. These compounds showed potent scavenging activity on diphenyl-p-picrylhydrazyl (DPPH) radical. Microsomal lipid peroxidation induced by Fe(I...