Agnes Bodanszky

A preferred conformation in the vasoactive intestinal peptide (VIP). Molecular architecture of gastrointestinal hormones

Abstract The ORD spectrum of the vasoactive intestinal peptide (VIP) in water indicates a preferred conformation with low helix content. Addition of organic solvents, especially of trifluoroethanol, results, even at low solvent concentration, in spectra with pronounced helical character. The readiness of shorter chains, with C-terminal sequences of VIP, to take up helical conformation under the effect of organic solvents parallels their biological activity. This suggests that an “active architecture” may be required for the interaction between hormone and receptor.

Sepharose-avidin column for the binding of biotin or biotin-containing peptides

Avidin konnte an das Polysaccharid Sepharose 4B, das zuvor mit Bromcyan aktiviert wurde, gebunden werden. Um Biotin oder Biotin-haltige Peptide zu binden, erwies sich eine Sepharose-Avidin-Säule als besonders günstig.

Molecular architecture of peptide hormones optical rotatory dispersion of cholecystokinin-pancreozymin, bradykinin and 6-glycine bradykinin

Die optischen Rotationsspektren des intestinalen Hormons Cholecystokinin-Pancreozymin weisen, im Gegensatz zu denen des Secretins, auf das Fehlen bevorzugter Konformation und geben Einblick in den Zusammenhang zwischen molekularer Architektur und Hormonaktivität.

Conformation of peptides of the secretin-VIP-glucagon family in solution

The significance of a well defined molecular architecture in hormone receptor interaction and the methods available for the study of preferred conformations are discussed. The conformational freedom in glucagon is a major obstacle in the determination of its biologically relevant geometry. In the secretin molecule intramolecular forces generate a folded, partially helical conformation. In respect of long range cooperative interactions resulting in a compact molecule with secondary-tertiary structure secretin is similar to globular proteins. In VIP some characteristics of secretin and also of glucagon can be recognized. Further progress in conformation analysis can be expected from the study of rigid, cyclic analogs in which the biological activities of the parent hormones are retained or even enhanced. Such analogs have well defined conformations without external stabilization from membrane mimicking lipids. Therefore, they provide information on the biologically relevant geometry of the hormones and contribute also to our knowledge of receptor sites.

Microbial production of vitamin B12 antimetabolites: II. 2-Amino-4-keto-3-methylpentanoic acids from bacillus cereus 439

Abstract 2-Amino-4-keto-3-methylpentanoic acids were isolated as a diastereomeric mixture from Bacillus cereus 439 fermentations and found to be vitamin B 12 antimetabolites in a bioassay system based on the vitamin B 12 -requiring Escherichia coli (Davis 113-3). A similar diastereomeric mixture with bioactivity was synthesized by condensation of 2-bromo-3-butanone with sodio diethyl acetamidomalonate followed by hydrolysis with 6 N HCl and purification by ion-exchange chromatography. The growth inhibitory effects of the antimetabolite were reversed by vitamin B 12 , l -methionine, l -isoleucine, l -leucine, l -valine, and d -alanine.

Is the vasoactive intestinal peptide (VIP) a prohormone

Abstract The possibility that the vasoactive intestinal peptide (VIP) is a prohormone, which through enzymic fragmentation gives rise to shorter chains with, yet unknown, hormonal activities is suggested by the occurrence of two pairs of adjoining basic residues in its sequence. (A similar pattern can be recognized in proinsulin.) Synthesis of one of the hormone-candidates, l -pyroglutamyl- l -methionyl- l -alanyl- l -valyl- l -lysyl- l -lysyl- l -tyrosyl- l -leucyl- l -asparaginyl- l -seryl- l - valyl- l -leucyl- l -threoninamide corresponding to the C-terminal 13-peptide sequences of chicken VIP is reported.

Mikrobiologische Oxydation von Steroiden durch Cephalosporia

It was found that members of the Cephalosporium species transform steroids under the known conditions of microbiological oxydation. Cephalosporium subverticillatum is able to produceΔ 4-testoloactone from progesterone, but, in case of a longer fermentation period,Δ 4-androsten-3, 17-dione can be isolated from the broth.

Optical rotatory dispersion of proline-rich peptides from the venom ofBothrops jararaca

Die optische Rotationsdispersion mehrer prolinreicher Oligopeptide aus dem Gift der SchlangeBothrops jararaca wurde gemessen und mit jener von Oligoprolinen verglichen. Es konnte nur eine qualitative Beziehung zwischen der angedeuteten Strukturrigidität und der biologischen Wirksamkeit der Peptide festgestellt werden.

Removal of Protecting Groups

A solution of benzyloxycarbonyl-L-prolyl-L-leucyl-glycinamide [3] (41.8 g, 100 mmol) in methanol [4] (250 ml) is prepared in a 500 ml round bottom flask [5] provided with a magnetic stirrer, a gas inlet-outlet tube [6] and surrounded by a large evaporating dish [7]. The air is displaced by a slow stream of nitrogen and a 10% palladium-on-charcoal catalyst [8] (4.2 g = 0.42 g metal) is added. Once again a slow stream of nitrogen is led through the flask, for a few minutes, then the introduction of a slow stream of hydrogen is started. The catalyst is kept in suspension by vigorous stirring. The gas which escapes through the outlet tube [9] is led, from time to time, through a half-saturated filtered solution of Ba(OH)2 in water. When the evolutionof CO2 ceases the reaction mixture is warmed by a water bath of about 50 °C until no more CO2 can be detected [10] in the escaping gas. The reaction mixture is cooled to room temperature and the introduction of hydrogen is terminated. The remaining gas is displaced by nitrogen and the catalyst is removed by filtration [11], preferably under a blanket of nitrogen. The catalyst is washed with methanol (50 ml) and stored under water until it is discarded or regenerated. The filtrate is evaporated in vacuo [12] or under a stream of air in a well ventilated hood. The residue is dried in air and finally in a desiccator over P2O5 in vacuo. The tripeptide amide (hemihydrate) weighs 28.8 g (98%) and melts at 125–126 °C [13].

Reagents for Peptide Synthesis

A solution of tert.butanol (74.1 g = 94 ml, 1 mol) and quinoline (130 g = 119 ml, 1 mol) in dichloromethane (150 ml) is stirred while phenyl chlorocarbonate [2] (157 g = 126 ml, 1 mol) is added dropwise. The rate of addition is regulated to maintain the temperature of the reaction mixture between 38 and 41 °C. After overnight storage at room temperature enough water is added to dissolve the precipitated quinoline hydrochloride. The organic layer is separated and washed twice with water (60 ml each time) and with 5% hydrochloric acid (3 to 4 times, 60 ml each time). The solution is dried over MgSO4, the solvent removed by distillation and the crude tert.butyl phenyl carbonate distilled from a Claisen flask. At 0.5 mm it boils at 74–78 °C [3]. The yield is about 143 g (73%).