Heme compounds, in combination with a reducing agent and oxygen, can express various activities of cytochrome P-450 enzymes. In the present study it was found that a mixture of hemin and excess cysteine was able to degrade the insecticide DDT partially. The major products were three water-soluble, non-toxic conjugates of DDT metabolites with cysteine which had lost two or three of the five chlorine atoms of DDT per molecule and whose structures were elucidated by gas chromatography/mass spectrometry. In 0.05 M NH4HC03, pH 7.7/ ethanol ( 5 : 6 , by vol.), the degradation reaction catalyzed by the hemin-cysteine model system was at least 8 x lo4 times Faster than the uncatalyzed reaction. In the presence of a designed 24-residues polypeptide or p-casein, two DDT-binding proteins, an additional fourfold increase in the rate of DDT degradation was observed. Although the concentrations of DDT and cysteine occurring in an organism would be expected to be lower than those in the experiments described, the formation of water-soluble conjugates of DDT metabolites with cysteine (and other amino acids) could also play a role in metabolism and excretion of DDT in vivo.The objective of the present investigation was to develop a model system for DDT degradation and to study the influence of DDT-binding proteins, in particular a designed 24-residue polypeptide [l - [4]. Aerobic reactions catalyzed by (inducible) cytochrome P-450 enzymes yield mainly DDA [his@-chloropheny1)acetic acid, Fig. I], the principal urinary excretion product of DDT in mammals, and DCBP (p,p'-dichlorobenzophenone, Fig. 1) [5, 61. Conjugates of DDA were also isolated. One such product was found to be a covalent complex of DDA, aspartic acid, and serine obtained after administration of DDT or DDA in rats [7].The prosthetic group of cytochrome P-450 enzymes is heme whose ligation with a thiolate seems to be essential for activity [S, 91. It is known that the biological activities of these enzymes can be mimicked by model systems. A hemin-cysteine complex, for example, was shown to catalyze the hydroxylation of aniline, p-toluidine and other substrates in the presence of excess cysteine [lo -121; hematin, myoglobin, and hemoglobin were able to reduce alkyl halides to the corresponding alkanes in the presence of sodium dithionite [13,14].Correspondence to B. Gutte, Biochemisches Institut der Universitat Zurich, Winterthurerstrasse 190, CH-8057 Zurich, SwitzerlandAbbreviations. DDT, t,1,1 -trichloro-2,2-bis(p-chlorophenyl)-ethane; DDE, 1,1-dichloro-2,2-bis(pp-chlorophenyl)ethylene; DDD, 1 ,I -dichloro-2,2-bis(p-chlorophenyl)ethane; DDA, bis(p-chloropheny1)acetic acid; DCBP, p,p'-dichlorobenzophenone; Fmoc, fluorenylmethyloxycarbonyl; GC-MS, gas chromatography/mass spectrometry.Enzymes. Cytochrome P-450 enzymes (EC 1.14.14.1); /I-Dgalactosidase (EC 3.2.1.23).We found that the mixture of hemin and excess cysteine also mediated the degradation of DDT and that the rate of this reaction was increased by addition of a designed 24-residue DDT-binding polypeptide [l...

Peptide chemists are increasingly concerned with the synthesis of polypeptides of biological and medical interest. This article describes several important applications of synthetic peptides in biochemistry, molecular biology, immunology, and medicine. Synthetic peptides may be useful in structure-function studies of polypeptides, as peptide hormones and hormone analogues, in the preparation of cross-reacting antibodies, and in the design of novel enzymes. Peptide chemists can actively contribute to progress in these fields if they are aware of the current problems in the life sciences. Volume 24 -Number 9 September 1985 Pages 71 9 -798 A n g e w Chem. Inr. Ed. Engl. 24 (1985) 719-727 0 VCH Verlagsgesellschuft mhH. 0-6940 Weinheim. 1985 0570-0833/0909-0719 $ 02.50/0

Zunehmend beschäftigen sich Peptidchemiker mit der Synthese biologisch und medizinisch wichtiger Polypeptide. In diesem Aufsatz werden einige nützliche Anwendungen von synthetischen Peptiden in Biochemie, Molekularbiologie, Immunologie und Medizin beschrieben. Synthetische Peptide sind von Interesse für Untersuchungen über Struktur‐Funktions‐Beziehungen bei Polypeptiden, als Peptidhormone und Hormonanaloga, für die Herstellung kreuzreagierender Antikörper und für die Konstruktion neuer Enzyme. Peptidchemiker können zum Fortschritt in den biologischen und medizinischen Wissenschaften beitragen, wenn sie mit deren aktuellen Problemen vertraut sind.

No abstract