Double- and tetrawalled molecular umbrella-spermine conjugates (I and II) have been synthesized, and their binding to calf thymus DNA (CT-DNA), poly[d(AT)], and poly[d(GC)] compared with that of a single-walled analogue (III). At moderate salt concentrations (8 mM NaCl), I and II show significantly greater affinity toward each DNA, relative to III; at high salt concentrations (150 mM NaCl), strong binding of I and II (but not III) was maintained toward poly[d(GC)]. Examination of the influence of I-III on the melting behavior of poly[d(AT)] has provided strong evidence that the binding of I and II reflects highly cooperative interactions among DNA-bound conjugates and that the DNA duplex serves as a nucleation site for umbrella aggregation. The implications of these findings for the rational design of novel drug conjugates that operate at the nuclear level, and also novel transfection agents, are briefly discussed.

Chemical Phenomena↗

PubMedDate not supplied

Enhancing the "stickiness" of bile acids to cross-linked polymers: a bioconjugate approach to the design of bile acid sequestrants.

A series of cross-linked polymers have been synthesized by reaction of 2% cross-linked, chloromethylated polystyrene with a tertiary amine derivative (7) of cholic acid (prepared by reaction of cholic acid methyl ester with N,N-dimethyl-ethylenediamine), followed by exhaustive quaternization with trimethylamine. Increased loadings of 7 result in enhanced binding of taurocholate ion and a decrease in its rate of release upon exposure to 50 mM aqueous NaCl. Examination of particle-size effects indicates that film diffusion and particle diffusion both contribute to the observed kinetics. Interruption tests that were carried out confirmed that particle diffusion is kinetically important. The relevance of this bioconjugate approach to the design of bile acid sequestrants for the treatment of hypercholesterolemia is briefly discussed.

Anion Exchange Resins↗

PubMedDate not supplied

Small-scale field trial with neuraminidase vaccine.

An inactivated whole-virus vaccine was prepared from the influenza virus recombinant H0N2 and administered to two groups of subjects. A total of 1,200 subjects were vaccinated; comparable groups of subjects served as controls. From a portion of the vaccinees sera were obtained prior to vaccination and three to four weeks afterwards. Serological tests revealed development of or increase in the antibody against H0 in a great majority of the vaccinated subjects and against N2 in slightly more than half of them. Antibody response to H3 antigen was only rarely encountered. Approximately three months after vaccination an influenza epidemic caused by Victoria-like (H3N2) viruses broke out in Czechoslovakia. Numerous influenza cases occurred in the two populations followed. Morbidity was significantly lower among the vaccinated than among the control subjects, indicating a protective effect of the neuraminidase vaccine under field conditions.

Adolescent↗

PubMedDate not supplied

Antibody response in humans after administration of whole-virion and split vaccine prepared from two different influenza A/swine viruses.

Previous findings with sera of several different animal species had indicated a close antigenic similarity between the X53 recombinant (possessing both surface antigens of A/Swine/New Jersey/76 virus) and the A/Swine/Ann Arbor/31 (AA) virus (1). Since the latter virus grows much better in chick embryos than the former, we examined the possibility of using the Ann Arbor virus instead of X53 for inactivated vaccine production. The present paper describes our findings in sera of subjects immunized with either whole-virus or split vaccine prepared from AA virus.

Adolescent↗