Rigid linkers for bioactive peptides

Josef Vagner, Heather L. Handl, Yasunari Monguchi, Umasish Jana, Lucinda J. Begay, Eugene A Mash, Victor J Hruby, Robert J. Gillies

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Rigid linkers of variable length were used to connect two high-affinity Nle4-D-Phe7-α-melanocyte stimulating hormone (NDP-α-MSH) or two low-affinity MSH(4) ligands. The linked peptides were synthesized by solid-phase methods. Control experiments indicate there is little or no effect of these linkers on NDP-α-MSH or MSH-(4) binding to the human melanocortin 4 receptor (hMC4R). Tethering two high-affinity ligands gave no binding enhancement, while tethering two low-affinity ligands resulted in binding enhancement that decreased with increased linker length. Furthermore, for the low-affinity ligands, the enhancement of affinity is inversely proportional to the estimated molecular moments of inertia. These results are consistent with a model wherein binding is enhanced when the rate of ligand reattachment to the receptor is fast relative to the rate of ligand diffusion.

Original languageEnglish (US)
Pages (from-to)1545-1550
Number of pages6
JournalBioconjugate Chemistry
Volume17
Issue number6
DOIs
StatePublished - Nov 2006

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Peptides
Melanocyte-Stimulating Hormones
Ligands
Hormones
Experiments

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Vagner, J., Handl, H. L., Monguchi, Y., Jana, U., Begay, L. J., Mash, E. A., ... Gillies, R. J. (2006). Rigid linkers for bioactive peptides. Bioconjugate Chemistry, 17(6), 1545-1550. https://doi.org/10.1021/bc060154p

Rigid linkers for bioactive peptides. / Vagner, Josef; Handl, Heather L.; Monguchi, Yasunari; Jana, Umasish; Begay, Lucinda J.; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J.

In: Bioconjugate Chemistry, Vol. 17, No. 6, 11.2006, p. 1545-1550.

Research output: Contribution to journalArticle

Vagner, J, Handl, HL, Monguchi, Y, Jana, U, Begay, LJ, Mash, EA, Hruby, VJ & Gillies, RJ 2006, 'Rigid linkers for bioactive peptides', Bioconjugate Chemistry, vol. 17, no. 6, pp. 1545-1550. https://doi.org/10.1021/bc060154p
Vagner J, Handl HL, Monguchi Y, Jana U, Begay LJ, Mash EA et al. Rigid linkers for bioactive peptides. Bioconjugate Chemistry. 2006 Nov;17(6):1545-1550. https://doi.org/10.1021/bc060154p
Vagner, Josef ; Handl, Heather L. ; Monguchi, Yasunari ; Jana, Umasish ; Begay, Lucinda J. ; Mash, Eugene A ; Hruby, Victor J ; Gillies, Robert J. / Rigid linkers for bioactive peptides. In: Bioconjugate Chemistry. 2006 ; Vol. 17, No. 6. pp. 1545-1550.
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