A water-soluble ruthenium glycosylated porphyrin catalyst for carbenoid transfer reactions in aqueous media with applications in bioconjugation reactions.
Water-soluble [Ru(II)(4-Glc-TPP)(CO)] (1, 4-Glc-TPP = meso-tetrakis(4-(beta-D-glucosyl)phenyl)porphyrinato dianion) is an active catalyst for the following carbenoid transfer reactions in aqueous media with good selectivities and up to 100% conversions: intermolecular cyclopropanation of styrenes (up to 76% yield), intramolecular cyclopropanation of an allylic diazoacetate (68% yield), intramolecular ammonium/sulfonium ylide formation/[2,3]-sigmatroptic rearrangement reactions (up to 91% yield), and intermolecular carbenoid insertion into N-H bonds of primary arylamines (up to 83% yield). This ruthenium glycosylated porphyrin complex can selectively catalyze alkylation of the N-terminus of peptides (8 examples) and mediate N-terminal modification of proteins (four examples) using a fluorescent-tethered diazo compound (15). A fluorescent group was conjugated to ubiquitin via 1-catalyzed alkene cyclopropanation with 15 in aqueous solution in two steps: (1) incorporation of an alkenic group by the reaction of N-hydroxysuccinimide ester 19 with ubiquitin and (2) cyclopropanation of the alkene-tethered Lys(6) ubiquitin (23) with the fluorescent-labeled diazoacetate 15 in the presence of a catalytic amount of 1. The corresponding cyclopropanation product (24) was obtained with approximately 55% conversion based on MALDI-TOF mass spectrometry. The products 23, 24, and the N-terminal modified peptides and proteins were characterized by LC-MS/MS and/or SDS-PAGE analyses.
Ho
Chi-Ming
CM
Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
Zhang
Jun-Long
JL
Zhou
Cong-Ying
CY
Chan
On-Yee
OY
Yan
Jessie Jing
JJ
Zhang
Fu-Yi
FY
Huang
Jie-Sheng
JS
Che
Chi-Ming
CM
D000475:Alkenes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D002417:Cattle; D003521:Cyclopropanes / Q000737:chemistry; D006031:Glycosylation; D006859:Hydrogen / Q000737:chemistry; D008665:Metalloporphyrins / Q000737:chemistry*; D008958:Models, Molecular; D009584:Nitrogen / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D012995:Solubility; D013455:Sulfur / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D000475:Alkenes; D000588:Amines; D003521:Cyclopropanes; D008665:Metalloporphyrins; D011506:Proteins; D014867:Water; D013455:Sulfur; D012428:Ruthenium; D006859:Hydrogen; C030797:cyclopropane; D009584:Nitrogen