Rigid Linkers for Bioactive Peptides
- 28 September 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 17 (6), 1545-1550
- https://doi.org/10.1021/bc060154p
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.Keywords
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