UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

The role of nonspecific hydrophobic interactions in the biological activity of N epsilon-acyl derivatives of glucagon. Studies of conformation, receptor binding, and adenylate cyclase activation.

Carrey, EA; Epand, RM; (1982) The role of nonspecific hydrophobic interactions in the biological activity of N epsilon-acyl derivatives of glucagon. Studies of conformation, receptor binding, and adenylate cyclase activation. J Biol Chem , 257 (18) pp. 10624-10630. Gold open access

Abstract

Glucagon was acylated at position 12 using conditions favoring reaction with the epsilon-amino group of lysine. The N epsilon-acetyl, N epsilon-hexanoyl, and N epsilon-decanoyl derivatives were prepared and purified. Secondary structure as measured by circular dichroism was lower in all derivatives than in glucagon, both in 95% methanol and in 25 mM sodium dodecyl sulfate at pH 2 and pH 12. N epsilon-Acetyl glucagon was less active than the native hormone in a radioreceptor assay and higher concentrations of this derivative were required to stimulate the adenylate cyclase activity of rat liver plasma membranes. The maximal extent of cyclase activation by this derivative was less than that found with the native hormone. N epsilon-Hexanoyl glucagon and N epsilon-decanoyl glucagon had greater activity than N epsilon-acetyl glucagon in receptor binding as well as in adenylate cyclase activation, although these two derivatives were not as active as the native hormone. N epsilon-hexanoyl glucagon and N epsilon-decanoyl glucagon were more potent in receptor binding than in adenylate cyclase activation. From these results it appears that the positive charge of the epsilon-amino groups may have a specific role in obtaining maximal biological activity, while the acyl groups contribute to the nonspecific hydrophobic interactions between the hormone and its receptor. In addition, a possible relationship between stabilization of the amphipathic helix in solution and the activity of these and other N epsilon-derivatives of glucagon is discussed.

Type: Article
Title: The role of nonspecific hydrophobic interactions in the biological activity of N epsilon-acyl derivatives of glucagon. Studies of conformation, receptor binding, and adenylate cyclase activation.
Location: United States
Open access status: An open access publication
Keywords: Acylation, Adenylyl Cyclases, Animals, Cell Membrane, Circular Dichroism, Enzyme Activation, Glucagon, Kinetics, Liver, Male, Protein Conformation, Rats, Rats, Inbred Strains, Receptors, Cell Surface, Receptors, Glucagon, Structure-Activity Relationship
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH - Directors Office
URI: http://discovery.ucl.ac.uk/id/eprint/92137
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item