Two new peptides, designated thymosin 1P8 and thymosin (L, respectively, have been isolated and their amino acid sequences established. Thymosin (38, isolated from calf thymus fraction 5, has a mass of 4518 daltons and contains 39 amino acid residues, ofwhich 31 are identical to the corresponding amino acid residues in thymosin 4 isolated from the same source. The NH2

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A simple and efficient new method for the highly stereoselective (at C(17) and C (20)) introduction of steroid side chains which are suitably functionalized for further elaboration is presented. The ene reaction of (17 Z)-ethylidene steroids, which are readily obtained from 17-keto steroids via a Wittig reaction, with various enophiles such as formaldehyde and acrylate esters leads to useful intermediates which contain the natural steroid configuration at C (20). Catalytic hydrogenation of the d16-double bond occurs from the u-face to stereospecifically generate the correct configuration at C (17). An additional chiral center at C (23) is also introduced stereoselectively by the use of methyl 2-chloroacrylate as the enophile.In recent years, the discovery of biologically important new steroidal natural products containing modified cholesterol side chains [ 11 has stimulated much synthetic activity. We have been interested in developing practical new routes to the therapeutically valuable vitamin D3 metabolites [2] (25-hydroxy-, I , 25-dihydroxy-, and 24 R, 25-dihydroxycholecalciferol) and bile acids (chenodeoxycholic acid). For our purpose, 17-ketosteroids seemed ?specially attractive as starting materials because of their potential large-scale availability from microbial degradation of abundant plant steroids and because of the ease at which they can be further modified chemically or microbially At the outset of our research, the only known stereospecific steroid side chain synthesis made use of organopalladium intermediates [6]. In the interim, there appeared a synthesis which involved stereoselective alkyiation of an initially introduced 17-acetic acid ester side chain followed by conversion of the ester function to the C(21) methyl group [7]. More recently, the elaboration of pregnenolone derivatives (which would require additional steps to prepare from 17-keto steroids) by Carroll [S] and oxy-Cope [9] rearrangements have been reported.We describe here a new approach to the introduction of the dezired side chain utilizing, as the key step, an ene reaction of an appropriately substituted (17 Z)-

The ability of rabbit liver aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphatate-lyase, EC 4.1.2.13) and rabbit liver fructose-1,6-bisphosphatase (FruP2ase; D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) to partition into the gel phase of Ultrogel AcA 34 is decreased in a mixture of the two enzymes. Titration experiments indicate that a 1:1 complex is formed. The value for the distribution coefficient of the complex corresponds to a molecular mass of 300,000 daltons, the value expected for a dimer containing one mole of each enzyme protein. Complex formation was not observed when either liver enzyme was replaced by the corresponding isozyme from rabbit muscle. The susceptibility of liver Fru-Pease to limited proteolysis by subtilisin was reduced in the presence of liver aldolase, but not when the latter was replaced by muscle aldolase, suggesting that the conformation of Fru-P2ase is altered in the complex. Limited proteolysis of liver aldolase abolishes its ability both to form theterodimer and to protect Fru-P2ase from modification by subtilisin.In mammalian liver fructose-1,6-bisphosphate aldolase (D-fructose-1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase, EC 4.1.2.13) and fructose-1,6-bisphosphatase fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) catalyze successive reactions in gluconeogenesis. Both are found in the cytosol and, like other enzymes of glycolysis and gluconeogenesis, are considered to exist and function as independent entities. In recent years, however, evidence has been accumulating for loose interactions between cytosolic proteins and between these proteins and cellular matrices. Arnold et al. (1,2) have reported that several glycolytic enzymes of muscle, including aldolase and glyceraldehyde-3-phosphate dehydrogenase, tend to associate with muscle actin, and Clarke and Masters (3) have examined these interactions in detail under conditions of physiological ionic strength. In mammalian erythrocytes both aldolase (4, 5) and glyceraldehyde-3-phosphate dehydrogenase (6) bind to the major membrane polypeptide (band 3 polypeptide), suggesting that these enzymes may function as a membrane-bound complex. Kinetic and physicochemical evidence for an interaction between aldolase and glyceraldehyde-3-phosphate dehydrogenase purified from rabbit muscle has been reported by Keleti and his coworkers (7,8).It has been proposed (3, 9, 10) that weak interactions between soluble enzymes may play a role in metabolism, either by promoting substrate channeling, in the case of enzymes that catalyze successive reactions, or by the induction of conformation changes that alter their catalytic or regulatory properThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact. 3889 ties. Although direct evidence for subtle interactions has been difficult to obtain, the kinetic evidence for substrate channeling repo...

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