title: Semisynthetic insulin analogues modified in positions B24, B25 and B29.
abstract: New semisynthetic analogues of human insulin, modified in the C-terminal region of the B-chain, were prepared to refine our understanding of the importance of particular amino acid residues in the expression of hormone biological properties. The following insulin analogues were synthesized by trypsin-catalyzed peptide-bond formation between the C-terminal arginineB22 of des-octapeptide(B23-B30)-insulin and synthetic octapeptides with the epsilon-amino group of lysineB29 protected by a phenylacetyl group: [L-Lys(Pac)B29]insulin, [D-PheB24,B25,L-Lys(Pac)B29]insulin and [D-Phe(p-Et)B24, L-Lys(Pac)B29]insulin. Enzymatic deprotection using immobilized penicillin amidohydrolase yielded: human insulin, [D-PheB24,B25]insulin and [DPhe(p-Et)B24]-insulin. Biological in vitro potencies (specific binding to cultured human lymphocytes IM-9 and lipogenic potency in isolated rat adipocytes) of the semisynthetic analogues were estimated, ranging from 0.2 to 100% relative to porcine insulin.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic, Praha.
authors.forename: I
authors.initials: I
authors.lastname: Svoboda
authors.forename: D
authors.initials: D
authors.lastname: Brandenburg
authors.forename: T
authors.initials: T
authors.lastname: Barth
authors.forename: H G
authors.initials: HG
authors.lastname: Gattner
authors.forename: J
authors.initials: J
authors.lastname: Jirácek
authors.forename: J
authors.initials: J
authors.lastname: Velek
authors.forename: I
authors.initials: I
authors.lastname: Bláha
authors.forename: K
authors.initials: K
authors.lastname: Ubik
authors.forename: V
authors.initials: V
authors.lastname: Kasicka
authors.forename: J
authors.initials: J
authors.lastname: Pospísek
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics; D008214:Lymphocytes / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010399:Penicillin Amidase / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D007328:Insulin; D010455:Peptides; D011972:Receptor, Insulin; D010399:Penicillin Amidase; D008239:Lysine