An acid-cleavable linker stable at neutral pH that releases doxorubicin at lysosomal pH

A Kemp's triacid amide of doxorubicin (DOX), esterified at a second carboxyl, releases DOX at lysosomal pH at a reasonable rate but is extremely stable at neutral pH.     

Gel permeation chromatography of asymmetric proteins

The gel permeation chromatographic behavior of three asymmetric proteins—collagen, fibrinogen, and the prolate ellipsoid lysozyme—was investigated using a variety of gel and high-performance liquid chromatographic media of various pore sizes and a wide range of flow rates. The time dependency of the elution patterns for columns and the partitioning of proteins between solvent and gel phases in batch experiments show that the “anomalous” behavior of asymmetric proteins is explicable by the mechanism proposed by Y. Nozaki, N. M. Schechter, J. A. Reynolds, and C. Tanford (1976, Biochemistry15, 3884); i.e., that these proteins penetrate pores of a size comparable to the minor semiaxis of the protein by end-on insertion. Thus, native type I collagen behaves as if it were a spherical protein of radius 8.2 Å, fibrinogen has an apparent radius of 32.4 Å, and lysozyme has an apparent radius of 14.6 Å. The rate at which asymmetric proteins penetrate the gel interior, however, is slow compared to the rate of gel penetration by globular proteins. The end-on insertion mechanism predicts that given infinite time, asymmetric proteins will be included into that portion of the internal volume of the gel which their smallest projectional cross sections allow them to penetrate. A method is presented for extrapolating the elution volume of asymmetric proteins to infinitely slow flow rate; from this extrapolation, one can calculate the minor semiaxis of the protein.     

Sires influence fetal death in pigtailed macaques (Macaca nemestrina)

Computerized colony records were used to identify dams and sires whose reproductive histories while breeding in harem groups indicated high or low risk for producing fetal deaths. The monkeys were then singly caged and bred within and between risk conditions during 24- to 72-hour matings. Although the low- and high-risk sires did not differ in ability to achieve conceptions, the results revealed that reproductive history predicted subsequent fetal death rates, and sires made a substantial contribution. Overall, high-risk sires had a 4.86 times higher relative risk of producing fetal death than low-risk sires. Compared with this figure, high-risk dams had only a 2.64 times higher risk for fetal death than low-risk dams. The male effect was most evident in comparisons of between- and within-risk matings. Females with excellent reproductive histories experienced a threefold increase in fetal deaths when mated with high-risk males, whereas females with poor reproductive histories experienced almost a 50% reduction in fetal deaths when mated with low-risk males. The results show that male factors beyond fertility need to be considered when examining the causes of reproductive failure in captive primates.