Automated and manual deprotection methods for allyl/allyloxycarbonyl (Allyl/Alloc) were evaluated for the preparation of side-chain-to-side-chain cyclic peptides. Using a standard Allyl/Alloc deprotection method, a small library of cyclic peptides with lactam bridges (with seven amino acids) was prepared on an automatic peptide synthesizer. We demonstrate that the Guibe method for removing Allyl/Alloc protecting groups under specific neutral conditions [Pd(PPh3)4/PhSiH3)/DCM] can be a useful, efficient and reliable method for preparing long cyclic peptides on a resin. We have also manually synthesized a cyclic glucagon analogue containing 24 amino acid residues. These results demonstrated that properly controlled palladium-mediated deprotection of Allyl/Alloc protecting groups can be used to prepare cyclic peptides on the resin using an automated peptide synthesizer and cyclic peptides with a long chain.

No abstract

A previous study on the feeding responses of tsetse flies, Glossina morsitans morsitans, implicated the existence of allomonal barriers, both volatile and nonvolatile, on the nonpreferred host, waterbuck, Kobus defassa. In the present study, electroantennogram-active compounds in odors from waterbuck were compared with those of two preferred hosts of tsetse flies, buffalo, Syncerus caffer, and ox, Bos indicus. Odors from the three bovids were trapped on activated charcoal and/or reverse-phase (octadecyl bonded) silica and analyzed with a gas chromatography-linked electroantennographic detector (GC-EAD) and, where possible, identified by using gas chromatography-linked mass spectrometry (GC-MS) and chromatographic comparisons with authentic samples. The GC-EAD profiles (with G. m. morsitans antennae) of the odors of the two preferred hosts were comparable, comprising medium-chain, saturated or unsaturated aldehydes and phenols, with buffalo emitting a few more EAG-active aldehydes. Waterbuck odor gave a richer profile, consisting of fewer aldehydes but more phenolic components and a series of 2-ketones (C-C13) and delta-octalactone. This bovid also emits moderate amounts of C5-C9 straight-chain fatty acids, some of which were detected in buffalo and ox only in trace amounts. However, these did not elicit significant GC-EAD responses. Waterbuck profiles from the antennae of G. pallidipes showed broad similarity to those from G. m. morsitans, although the composition of aldehydes and ketones was somewhat different, indicating species-specific difference in the detection of host odors. Certain waterbuck-specific EAG-active components, particularly the 2-ketones and lactone, constitute a candidate allomonal blend in waterbuck odor.

The acetone extracts of the root bark and stem bark of Erythrina sacleuxii showed antiplasmodial activities against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Chromatographic separation of the acetone extract of the root bark afforded a new isoflavone, 7-hydroxy-4'-methoxy-3'-prenylisoflavone (trivial name 5-deoxy-3'-prenylbiochanin A) along with known isoflavonoids as the antiplasmodial principles. Flavonoids and isoflavonoids isolated from the stem bark of E. sacleuxii were also tested and showed antiplasmodial activities. The structures were determined on the basis of spectroscopic evidence.

In search for the bioactive conformation of glucagon, "positional cyclization scanning" was used to determine secondary structures of glucagon required for maximal interaction with the glucagon receptor. Because glucagon is flexible in nature, its bioactive conformation is not known except for an amphiphilic helical conformation at the C-terminal region. To understand the conformational requirement for the N-terminal region that appears to be essential for signal transduction, a series of glucagon analogues conformationally constrained by disulfide or lactam bridges have been designed and synthesized. The conformational restrictions via disulfide bridges between cysteine i and cysteine i + 5, or lactam bridges between lysine i and glutamic acid i + 4, were applied to induce and stabilize certain corresponding secondary structures. The results from the binding assays showed that all the cyclic analogues with disulfide bridges bound to the receptor with significantly reduced binding affinities compared to their linear counterparts. On the contrary, glucagon analogues containing lactam bridges, in particular, c[Lys(5), Glu(9)]glucagon amide (10) and c[Lys(17), Glu(21)]glucagon amide (14), demonstrated more than 7-fold increased receptor binding affinities than native glucagon. These results suggest that the bioactive conformation of glucagon may adopt a helical conformation at the N-terminal region as well as the C-terminal region, which was not evident from earlier biophysical studies of glucagon.

No abstract

Seven alkaloids have been isolated from Teclea trichocarpa including four, normelicopicine (1), arborinine (2), skimmianine (6), and dictamnine (7), that are reported for the first time in addition to the previously reported alkaloids melicopicine (3), tecleanthine (4), and 6-methoxytecleanthine (5). The structure of 1 was confirmed by single-crystal X-ray crystallography. Two alkaloids, 1 and 2, displayed limited in vitro activities against Plasmodium falciparum strains HB3 and K1, but there appeared to be little cross-resistance with chloroquine. Alkaloid 1 was found to have some activity against P. berghei in mice (32% suppression of parasitaemia at a dose of 25 mg x kg(-1) x day(-1)), but unlike chloroquine it did not inhibit beta-haematin formation in a cell-free system; 1 was found to have low in vitro cytotoxicity to KB cells (IC50 > 328 microM).

ABSTRACT.ABSTRACT. ABSTRACT. ABSTRACT. A new pterocarpan (named 8-methoxyneorautenol) was isolated from the acetone extract of the root bark of Erythrina abyssinica. In addition, the known isoflavonoid derivatives eryvarin L, erycristagallin and shinpterocarpin were identified for the first time from the roots of this plant. The structures were determined on the basis of spectroscopic evidence. The new compound showed selective antimicrobial activity against Trichophyton mentagrophytes. The acetone extract of the root bark of E. abyssinica showed radical scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl radical (DPPH). The pterocarpenes, 3-hydroxy-9-methoxy-10-(3,3-dimethylallyl)pterocarpene and erycristagallin, were the most active constituents of the roots of this plant and showing dose-dependent activities similar to that of the standard quercetin.