In order to increase the retention of drug activity, regiospecific coupling has been used to synthesize conjugates of methotrexate (MTX, 1) with normal rabbit IgG (NRG) and a mouse anti-human renal cancer monoclonal IgG (Dal K-20). MTX gamma-methyl ester (4) was produced either by selective esterification of MTX or by coupling of 4-amino-4-deoxy-N10-methylpteroic acid (2) with suitable glutamic acid derivatives. The MTX gamma-methyl ester (4) was then converted to the corresponding hydrazide 6. An amide-linked conjugate was formed when the MTX gamma-hydrazide (6) was converted to reactive acylating species 7 by using tert-butyl nitrite or trifluoroacetaldehyde, which were reacted with nucleophilic centers, presumably epsilon-amino groups, in native IgG. A hydrazone-linked conjugate was formed when MTX gamma-hydrazide (6) was reacted directly with IgG that had first been oxidized with periodate to form polyaldehyde IgG. The regiospecifically synthesized conjugates were somewhat more effective inhibitors in vitro of dihydrofolate reductase and of colony formation by human renal cancer (Caki-1) cells than were control nonregiospecific conjugates.

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An "optimum acidity" range for fruit jelly-making by the hot method has been reported by different workers. Tarr1 has attached pectin-acid compound significance to this and supports his hypothesis by a series of experiments in which the number of cc. of different acids required to give a definite

The spectrogram of apple pectin ash with which we worked gave the lines of the following elements: Na, K, Ca, Mg, Fe, Al, Mn, Si, and P. Chemical analysis shows the presence of chlorides, sulphates, carbonates and organic acid anions. According to Wiley, 56y0 of the ash of apples, expressed as oxides, is potassium, 9% is phosphorus; Mg, Ca, S, are each present in the neighborhood of 3 7 0 ; the other elements are present in quantities less than one per cent.There are three recognized methods for removing electrolyte impurities from colloid sols: electrodialysis ; reprecipitation; washing by decantation with a non-peptizing solvent. Methods of PurificationReprecipitatzon by Alcohol: Taking ash content as criterion of efficiency, reprecipitation by alcohol is, in our opinion, the least satisfactory of the three

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