Biological Chemistry Hoppe-Seyler · 1994 · 14 citations · 13 references
Life SciencesBiochemistryEndocrinologyEnzymologyHormone BiochemistryProtein BiochemistryAmino Acid ChemistryEnzymatic Cleavage StrategiesPeptide ChemistryPeptide Hormone BiochemistryProteolytic EnzymesProteolytic ProcessingD-amino Acid PeptidesEnzymatic DeprotectionHuman InsulinHydrolytic DeprotectionInsulin BiochemistryPeptide Hormone StructureProtein HormonesSelective Deprotection
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.
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Monomeric insulins obtained by protein engineering and their medical implications
Jens Brange, Ulla Ribel, J. F. Hansen et al. · Nature · 1988 · 493 citations
Enzyme-assisted semisynthesis of human insulin
Ken Inouye, Kunio Watanabe, Kazuyuki Morihara et al. · Journal of the American Chemical Society · 1979 · 144 citations