Semisynthetic insulin analogues modified in positions B24, B25 and B29
Language English Country Germany Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Amino Acids analysis MeSH
- Chromatography, Ion Exchange MeSH
- Mass Spectrometry MeSH
- Insulin analogs & derivatives chemistry pharmacokinetics MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Lymphocytes metabolism MeSH
- Lysine chemistry MeSH
- Molecular Sequence Data MeSH
- Penicillin Amidase chemistry MeSH
- Peptides chemical synthesis MeSH
- Receptor, Insulin metabolism MeSH
- Amino Acid Sequence MeSH
- Adipocytes metabolism MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amino Acids MeSH
- Insulin MeSH
- Lysine MeSH
- Penicillin Amidase MeSH
- Peptides MeSH
- Receptor, Insulin MeSH
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.
References provided by Crossref.org
Structural integrity of the B24 site in human insulin is important for hormone functionality
