Biomedical subjects

H Zahn

Publications and source records attributed to H Zahn.

At least 55 records · Page 3Linked to original sources

PubMed1976

[Aminolysis and racemization of activated esters with the use of high temperatures (author's transl)].

The reactivities in aminolysis of the benzyl, phenyl, p-nitrophenyl and pentachlorophenyl esters of benzyloxycarbonylphenylalanine were ascertained at different temperatures up to 90 degrees C and the occurrence of racemization investigated. It turned out that the protective function of the benzyloxycarbonyl group in relation to the racemization was conserved, even at the high temperatures used in the peptide synthesis.

Carboxylic Acids↗

PubMed1975

B-chain shortening of matrix-bound insulin with pepsin, II. Preparation and properties of camel des-pentapeptide (B26-30)- and des-PheB1-des-pentapeptide (B26-30)- insulin.

Digestion of matrix-bound camel insulin with pepsin was found to be restricted to the cleavage of the peptide bond between phenylalanine(B25) and tyrosine(B26). Purification of the camel des-pentapeptide(B26-30)-insulin obtained was achieved by gel filtration and ion exchange chromatography, yielding a molecularly uniform product. In the same way, camel des-PheB1-insulin prepared according to a method described for bovine insulin was hydrolyzed with pepsin and purified to give the des-PheB1-despentapeptide(B26-30)-insulin. The biological activity of these modified camel insulins was found to be as much reduced as the corresponding bovine insulin analogues. However, the reduced biological activity of camel des-PheB1-insulin (60%) was a contrast to the fully active bovine des-PheB1-insulin.

Amino Acids↗

PubMed1975

[Insulin analogues with permuted A chain N-terminus (author's transl)].

By partial synthesis insulin analogues were prepared in which the amino acid in position 1 of the A chain was permuted. Glycine in position A 1 was exchanged for leucine, tert.- butyloxycarbonylvaline, valine, proline, lysine as well as glutamic acid. Two pathways of partial synthesis were followed: Firstly, des-1-glycine-A-chain S-sulfonate was reacted with active esters of tert.-butyloxycarbonylamino acids. The ensuing modified A-chains were combined with natural B-chain to give A1-permuted insulins. In the second procedure, the preparation of tris-Boc-[A1-leucine]insulin was accomplished by reaction of Boc-leucine N-hydroxysuccinimide ester with NalphaB1,NepsilonB29-bis(tert.-butyloxycarbonyl)-des-A1-glycine-insulin. The protected insulin derivative had been prepared by combination of des-glycine-A-chain with Nalpha1,Nepsilon29-bis(tert.-butyloxycarbonyl)-B-chain. The deprotected analogues differed considerably in their CD-spectra from insulin and possessed low in vitro biological activities of 2.5-17%. Crystallization attempts failed. Thus, the introduction of side chains in position A1 distorts the conformation sterically and decreases the biological activity.

Amino Acid Sequence↗

PubMed1975

[Semisynthetic sheep des-A1-glycine insulin (author's transl)].

The synthetic Des-1-glycine-A-chain of sheep insulin as the monomeric cyclic bisdisulfide and native bovine B-chain bissulfonate were reduced together with mercaptoethanol. They combined at pH 10.6 to yield Des-A1-glycine-insulin. This was purified by gel and ion exchange chromatography. The low insulin activity (0.4 - 0.6%) as measured by the fat cell test as well as the change in the CD spectrum indicated that the loss of the N-terminal glycine of the A-chain results in fully inactive insulin. This confirms the results obtained earlier by partial synthesis of Des-A1-glycine-insulin.

Animals↗

PubMed1975

[Partial synthesis and properties of des-A1-glycine-insulin (author's transl)].

Des-Gly-A-chain-tetra-S-sulphonate was prepared by Edman degradation following two different routes. A) Via complete reaction of A-chain from bovine insulin with 150 equivalents of phenylisothiocyanate in pyridine/water and trifluoroacetic acid cleavage of the resulting phenylthiocarbamoyl A-chain. B) Via reaction of bovine insulin with about 20 equivalents of phenylisothiocyanate until a substitution degree of 2.3-2.5 was reached, trifluoroacetic acid cleavage of the crude derivatives and oxidative sulphitolysis of the resulting desaminoacyl insulins. Preparative electrophoresis (pH 2) or ion exchange chromatography using DEAE-Sephadex gave des-Gly-A-chain in a yield of 60-65% of theory according to method B, containing less than 1% of glycine. Des-GlyA1-insulin was prepared by combination with 0.67 equivalents of B-chain-bis-S-sulphonate and isolated in yields of 5-13%, based on B-chain, after gel filtration (pH 8) and ion exchange chromatography (CM-cellulose, pH 3-2). The electrophoretically (pH 2 and 8.6) homogeneous analogue did not crystallize in the presence of zinc ions. Its blood sugar lowering potency is 10-25%, its in vitro insulin activity (fat cell assay) only 1-2%. The immunoreactivity against anti-insulin sera in different test systems is markedly reduced. There are clear differences between the CD-spectra of des-Gly-insulin and insulin, indicating a loss of ordered secondary structure. From the results it is concluded that structure-stabilizing non covalent bonds are abolished by the removal of the invariant A1-glycine. This leads to conformational alterations which cause the far-going inactivation of the molecule.

Amino Acid Sequence↗

PubMed1975