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Application of Metal‐Free Triazole Formation in the Synthesis of Cyclic RGD–DTPA Conjugates
Author(s) -
van Berkel Sander S.,
Dirks A. Ton J.,
Meeuwissen Silvie A.,
Pingen Dennis L. L.,
Boerman Otto C.,
Laverman Peter,
van Delft Floris L.,
Cornelissen Jeroen J. L. M.,
Rutjes Floris P. J. T.
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800074
Subject(s) - cycloaddition , conjugate , chemistry , combinatorial chemistry , triazole , tandem , click chemistry , aqueous solution , trifluoromethyl , metal , stereochemistry , organic chemistry , materials science , catalysis , mathematical analysis , alkyl , mathematics , composite material
The tandem 1,3‐dipolar cycloaddition‐retro‐Diels–Alder (tandem crDA) reaction is presented as a versatile method for metal‐free chemoselective conjugation of a DTPA radiolabel to N ‐δ‐azido‐cyclo(‐Arg‐Gly‐Asp‐ d‐ Phe‐Orn‐) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl‐substituted oxanorbornadiene derivatives in the 1,3‐dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio‐orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111 In‐labeled c(RGD)‐CF 3 ‐triazole‐DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for α v β 3 (IC 50 =192 n M ) and favorable pharmacokinetics.