Oligoproline helices as structurally defined scaffolds for oligomeric G protein-coupled receptor ligands.
Oligoprolines (OPs) are used as rigid backbone scaffolds for the design of oligomeric ligands that target specific G protein-coupled receptors. The OPs were designed to vary in length, the position and number of the ligand-functionalized residues incorporated. For all synthesized compounds a typical PP type II helix was evidenced by circular dichroism indicating that decoration of the helix with large ligands did not affect the helical conformation. Pharmacological evaluation revealed that oligomerization of an agonist with the use of an oligoproline scaffold showed an increase in potency when compared to the monomeric counterparts.
Bonger
Kimberly M
KM
Leiden Institute of Chemistry, Department of Bio-organic Synthesis, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Kapoerchan
Varsha V
VV
Grotenbreg
Gijsbert M
GM
van Koppen
Chris J
CJ
Timmers
C Marco
CM
van der Marel
Gijsbert A
GA
Overkleeft
Herman S
HS
D002942:Circular Dichroism; D006801:Humans; D008024:Ligands; D011392:Proline / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D011974:Receptors, LH / Q000819:agonists* / Q000378:metabolism*
D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; D011392:Proline