These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Disposition of the phenylalanine B25 side chain during insulin-receptor and insulin-insulin interactions.
    Author: Mirmira RG, Tager HS.
    Journal: Biochemistry; 1991 Aug 20; 30(33):8222-9. PubMed ID: 1868095.
    Abstract:
    By the semisynthesis of both full-length insulin analogues and their des-pentapeptide-(B26-B30)-alpha-carboxamide counterparts, we have examined the importance of the electronic character and bulk of the position B25 side chain both in directing insulin interaction with its receptor on isolated canine hepatocytes and in determining the ability of insulin to self-associate in solution. Analogues include those in which PheB25 was replaced by cyclohexyl-Ala; Tyr; p-nitro-, p-fluoro-, p-iodo-, or p-amino-Phe; or p-amino-Phe in which the aromatic amino function had been acylated by the acetyl, hexanoyl, decanoyl, or 1-adamantanoyl group. Our findings identify that (a) the beta-aromatic side chain at position B25 is indeed critical for high-affinity ligand-receptor interactions, (b) neither electron withdrawal from nor electron donation to the beta-aromatic ring perturbs ligand-receptor interactions in major ways, (c) considerable latitude is allowed the placement of linear or polycyclic apolar mass at the para position in p-amino-PheB25-substituted analogues with respect both to receptor binding affinity and to biological activity in vivo, and (d) para apolar mass at position B25 is readily accommodated during the self-association of insulin monomers, as assessed by analytical tyrosine radioiodination and spectroscopic analysis of analogue complexes with Co2+ and Co3+. These findings are discussed in terms of a model for insulin-receptor interactions at the cell membrane in which the position B25 side chain defines the edge of intermolecular contact.
    [Abstract] [Full Text] [Related] [New Search]