192212-24-1Relevant articles and documents
A novel radioiodination reagent for protein radiopharmaceuticals with L- lysine as a plasma-stable metabolizable linkage to liberate m-iodohippuric acid after lysosomal proteolysis
Wakisaka, Kouji,Arano, Yasushi,Uezono, Takashi,Akizawa, Hiromichi,Ono, Masahiro,Kawai, Keiichi,Ohomomo, Yoshiro,Nakayama, Morio,Saji, Hideo
, p. 2643 - 2652 (1997)
Radiochemical design of polypeptides using metabolizable linkages would be attractive to enhance target-selective localization of radioactivity for diagnostic and therapeutic nuclear medicine. However, while use of ester bonds as the linkage allows selective release of the designed radiometabolite from covalently conjugated polypeptide after lysosomal proteolysis in nontarget tissues, low plasma stability of ester bonds causes a decrease in radioactivity levels of the target. In pursuit of new metabolizable linkages that provide stable attachment of radiolabels with polypeptide in plasma while facilitating rapid and selective release of designed radiometabolites of rapid urinary excretion in lysosomes, a new radioiodination reagent with L-lysine as the metabolizable linkage to liberate m-iodohippuric acid (L- HML) was designed and synthesized. Stabilities of the metabolizable linkage in serum and cleavabilities of the linkage in lysosomal proteloysis in hepatic cells were investigated after conjugation of [131I]-L-HML iwht galactosyl-neoglycoalbumin (NGA). For comparison, a radioiodination reagent with an ester bond to release m-iodohippuric acid (MIH) was conjugated with NGA under similar conditions. When incubated in human serum, [131I-L-HML- NGA liberated less than 3% of the initial radioactivity after 24 h, whereas [125I]MIH-NGA released more than 60% of its radioactivity during the same interval. In biodistribution studies, [131I]-L-HML-NGA demonstrated radioactivity elimination from murien liver at a rate and excretion route similar to [125I]MIH-NGA. Analyses of murine urine after injection of [131I]-L-HML-NGA indicated a single radioactivity peak at fractions identical to those of m-iodohippuric acid. Biodistribution studies of radioiodinated NGAs with D-lysine or cadaverine as the linkages demonstrated a delayed elimination rate from murine liver with significantly higher radioactivity being excreted in the feces at 24 h postinjection. Thus, L-HML is the first reagent that allows stable attachment of radiolabel with polypeptide in serum while facilitating selective release of a radiometabolite with rapid urinary excretion from covalently conjugated polypeptides after lysosomal proteolysis at a rate similar to that of ester bonds. Thus, L-HML is potentially useful for the radioiodination of polypeptides for diagnostic and therapeutic purposes.
CONJUGATES
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, (2020/07/14)
The present invention provides a conjugate of formula (I) and itsuse in methods of treatment, and also methods for delivering an active agent into a cell. The methods may be used to deliver an active agent into a nematode, flatworm, parasite or bacterium. The conjugate of formula (I) is: (formula (I)), wherein -D- is C1-4 alkylene or C2-4 alkenylene, preferably C2-4 alkenylene, where the alkylene or alkenylene is optionally substituted with alkyl or halo; A- is an active agent for delivery; and -RA, -RB, -RT1, -RT2, -R1, -R2, -R3, -X- and -L- are as defined herein.
CARBON MONOXIDE RELEASING NORBORNENONE COMPOUNDS
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Page/Page column 56; 118; 119, (2017/09/27)
The present invention provides organic compounds which are capable of releasing carbon monoxide under physiological conditions or pH trigger, and to the use of such compounds for conditioning a cell, tissue or organ, for example, to protect against ischaemic injury during a transplant event.
ANTI-STAPHYLOCOCCUS AUREUS ANTIBODY RIFAMYCIN CONJUGATES AND USES THEREOF
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Page/Page column 123, (2016/06/28)
The invention provides anti-Staphylococcus aureus antibody rifamycin antibiotic conjugates and methods of using same.
