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PubMed · 17105235

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
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Abstract

Rigid linkers of variable length were used to connect two high-affinity Nle4-D-Phe7-alpha-melanocyte stimulating hormone (NDP-alpha-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-alpha-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.

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Cell LineCross-Linking ReagentsDimerizationHumansLigandsMolecular StructurePeptidesProtein BindingReceptor, Melanocortin, Type 4Journal ArticleResearch Support, N.I.H., Extramural

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Josef Vagner, Heather L Handl, Yasunari Monguchi, Umasish Jana, Lucinda J Begay, Eugene A Mash, Victor J Hruby, Robert J Gillies. Rigid linkers for bioactive peptides.. https://doi.org/10.1021/bc060154p

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