The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel semisynthetic insulin analogs
Language English Country England, Great Britain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
17436342
DOI
10.1002/psc.847
Knihovny.cz E-resources
- MeSH
- Insulin analogs & derivatives chemical synthesis metabolism pharmacology MeSH
- Rats MeSH
- Humans MeSH
- Oligopeptides chemistry metabolism pharmacology MeSH
- Penicillin Amidase chemistry MeSH
- Rats, Wistar MeSH
- Receptor, Insulin metabolism MeSH
- Protein Binding physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Insulin MeSH
- Oligopeptides MeSH
- Penicillin Amidase MeSH
- Receptor, Insulin MeSH
In this paper, we present the detailed synthetic protocol and characterization of Fmoc-Lys(Pac)-OH, its use for the preparation of octapeptides H-Gly-Phe-Tyr-N-MePhe-Thr-Lys(Pac)-Pro-Thr-OH and H-Gly-Phe-Phe-His-Thr-Pro-Lys(Pac)-Thr-OH by solid-phase synthesis, trypsin-catalyzed condensation of these octapeptides with desoctapeptide(B23-B30)-insulin, and penicillin G acylase catalyzed cleavage of phenylacetyl (Pac) group from Nepsilon-amino group of lysine to give novel insulin analogs [TyrB25, N-MePheB26,LysB28,ProB29]-insulin and [HisB26]-insulin. These new analogs display 4 and 78% binding affinity respectively to insulin receptor in rat adipose membranes.
References provided by Crossref.org
Rational steering of insulin binding specificity by intra-chain chemical crosslinking
Structural integrity of the B24 site in human insulin is important for hormone functionality
Non-equivalent role of inter- and intramolecular hydrogen bonds in the insulin dimer interface
