POLYPEPTIDE MODELS OF COLLAGEN. SYNTHESIS OF (PRO-PRO-β-ALA)n

The sequential copolymer (Pro-Pro-β-Ala)_n has been synthesized as a model for collagen. Preliminary studies indicate that the polymer may bear conformational resemblance to collagen.     

Enzymatic formation of chemically reactive metabolites of N-nitrosodesmethyl tripelennamine by a mechanism other than N-dealkylation.

Benzyl-¹⁴C and N-methyl-³H labeled N-nitroso derivatives (NDT) of tripelennamine were synthesized by reacting the corresponding labeled parent drug with sodium nitrite at pH 1–2, and their covalent binding to rat liver musomes was compared with that of radiolabeled tripelennamine. The covalent binding of these substances is mediated by liver musomal cytochrome P-450 enzymes; it required an NADPH-generating system and oxygen, and was inhibited by CO:O₂ (8:2). Reduced glutathione (1 mM) also inhibited the covalent binding. The covalent binding of NDT to liver musomal proteins from phenobarbital-pretreated rats was ten times greater than that of tripelennamine. A K_m of 60 μM and a V_max of 1 nmole/mg of protein/min were obtained for the covalent binding of NDT. Phenobarbital and acetone pretreatments of rats increased covalent binding of both the drug and its nitroso derivative, while pretreatment with 3-methyl-cholanthrene decreased their binding. These results suggest that chemically reactive intermediates of tripelennamine and NDT are involved in the covalent binding. Under the conditions in vitro employed, the rate of N-demethylation of NDT was lower than that of the parent drug. Moreover, the covalent binding of the N-methyl-³H labeled nitroso derivative was equivalent to that of the benzyl-¹⁴C labeled derivative. Thus, N-demethylation is not a requisite for the covalent binding of tripelennamine and its N-nitroso derivative. The mechanism of the covalent binding of the N-nitroso derivative of tripelennamine, therefore, differs from that of dimethylnitrosamine.     

Invluence of oral contraceptives on circulating immune response. II. Effect of progestogenic and estrogenic components

Female mice were treated with chlormadinone acetate (.25 mcg or 6.25 mcg), megestraol acetate (.25 mcg or 6.25 mcg), ethynodiol diacetate (.5 mcg or 12.5 mcg), norgestrel (.25 mcg or 6.25 mcg) or norethynodrel (2.5 mcg or 62.5 mcg) and studied to determine what effect these progestagens had on circulating tetanus antibody titers. None of the progesterones affected the immune response to tetanus toxoid. Mice given ethinyl estradiol or mestranol had enhanced circulating antibody titers. It is conlcuded that combination oral contraceptives act to diminish antibody response as a result of the combined potency of the estrogen and progesterone components.