CHEMICAL SYNTHESIS OF [DES(TETRAPEPTIDE B27–30), TYR(NH2)26-B] AND [DES(PENTAPEPTIDE B26–30), PHE(NH2)25-B] BOVINE INSULINS*

Two analogs of bovine insulin, [des(tetrapeptide B^27–30), Tyr(NH₂)²⁶-B] and [des(pentapeptide B^26–30), Phe(NH₂)²⁵-B] insulin, which differ from the parent molecule in that the C-terminal tetrapeptide and pentapeptide sequences, respectively, from the B chain have been eliminated and the newly exposed residues are amidated, have been synthesized. The [des(tetrapeptide B^27–30), Tyr(NH₂)²⁶-B] insulin shows potencies of 16.8 IU/mg by the mouse convulsion assay method and 10.8 IU/mg by the radioimmunoassay method. The [des(pentapeptide B^26–30), Phe(NH₂)²⁵-B] insulin possesses a potency of 10.5 IU/mg when assayed by the mouse convulsion method and 14 IU/mg by the radioimmunoassay technique. The potencies of these analogs are higher than the potencies of the respective non-amidated derivatives (Katsoyannis et al., 1973, 1974). It is speculated that the gradual decline of biological activity observed as amino acid residues are eliminated from the C-terminal region of the B chain of insulin is due to the proximity of a hydrophilic carboxyl group to the hydrophobic core of the protein molecule.     

Correlation of hepatitis B surface antigen clearance with the route of hepatitis B virus infection

We studied 563 consecutive adults with acute hepatitis B hospitalized from May 1981 to May 1983 and their habitual heterosexual partners. Radio-immunoassays for the detection of serological markers of hepatitis A virus (HAV) and hepatitis B virus (HBV) and enzyme-immunoassay for the detection of IgM antibody to hepatitis B core antigen (IgM anti-HBc) were used. Of the 563 patients, 503 (89.7%) were hepatitis B surface antigen (HBsAg) positive and 60 (10.7%) were HBsAg negative on admission. Absence of HBsAg on admission was observed significantly more frequently in patients infected possibly by the heterosexual route than in the remaining patients (23.3% versus 6.6%; P less than 0.001). This finding was independent of sex. These data show that the route of HBV infection rather than the sex appears to have a more important role in the rapid clearance of HBsAg.     

[21 - ARGININE - A] INSULIN

An analog of sheep insulin which differs from the parent molecule in that the C-terminal amino acid residue of the A chain, asparagine, is replaced by arginine, has been synthesized and isolated in highly purified form. The [Arg²¹] A chain of sheep insulin was synthesized by the fragment condensation approach and isolated as the S-sulfonated derivative. Conversion of the latter into the sulfhydryl form and interaction with the S-sulfonated B chain of bovine (sheep) insulin yielded [Arg²¹-A] sheep insulin, which was purified by chromatography on a carboxymethylcellulose column with an exponential sodium chloride gradient. The [Arg²¹-A] sheep insulin shows potencies of 10.5–12.5 IU/mg when assayed by the mouse convulsion method and 8.6 IU/mg by the radioimmunoassay method (cf. 23–25 IU/mg for the natural hormone). It has been suggested that in the insulin molecule the A²¹ asparagine participates in salt bridge- and hydrogen bond-forming interactions which are critical in the biological activity of the hormone. Although the [Arg²¹-A] analog still retains these interactions, it is only ca. 50% as active as the natural hormone. It is speculated that other factors than the abovementioned interactions come into play, which involve the side chain of the A²¹ amino acid residue and affect the biological activity of the hormone.