Synthesis and characterization of fluorinated homocysteine derivatives as potential molecular probes for 19 F magnetic resonance spectroscopy and imaging

Design of protein homocystamides with enhanced tumor uptake properties for 19F magnetic resonance imaging

“…We have previously reported on implementing thiolactones as functional handles for fluorinated protein conjugate synthesis. 48 In this work we used the same approach to obtain a novel fluorinated albumin conjugate, PFT-Hcy-HSA (Figure 2). A comparative in vitro study between already reported and new compounds was performed.…”

“…48 In this work, to explore the chemistry of albumin site-specific labeling using N-perfluorotoluenesubstituted HTL (PFT-HTL), we synthesized fluorinated albumin conjugate PFT-Hcy-HSA ( Figure 2). The homocysteinylation of albumin with PFT-HTL was carried out according to the procedure described in Experimental procedures section.…”

“…Therefore, it is possible to find optimal conditions for site-specific introduction of fluorine labels into the protein via its N-homocysteinylation by fluorinated HTL derivatives. Earlier, 48 our group has synthesized a fluorinated HTL (Ntrifluoroacetyl homocysteine thiolactone, CF 3 C(O)-HTL) that readily and irreversibly reacts with -amino groups of albumin's lysine residues ( Figure 1). In the present work, we have synthesized and characterized a novel conjugate of HTL with perfluorotoluene (PFT).…”

“…We suggest taking advantage of natural posttranslational modification of albumin -its Nhomocysteinylation 47 -to use the amino group of the homocysteine (Hcy) residue as a site of fluorine label attachment to the protein. 48 N-Homocysteinylation of HSA by homocysteine thiolactone (HTL) in vivo involves modification of only three of the 59 protein lysine residues (Lys-525, Lys-137 and Lys-212). 49 On the other hand, eight different lysine modifications sites (Lys-525, Lys-212, Lys-205, Lys-159, Lys-137, Lys-12 and Lys-4) were identified in vitro, suggesting that the preferred site of modification is dependent on the HTL concentration.…”

One-Pot Double Modification of Polymers Based on Thiolactone Chemistry

“…Because the intrinsic instability of the neutral homocysteine-γ-thiolactone 1 leads to the formation of the corresponding diketopiperazine adduct [79], an efficient reaction between the amino group in the α-position and an electrophile is mandatory, eventually leading to the targeted monomer or initiator. Amidation reactions are most frequently used: conjugation with acid halides [80][81][82][83], (in situ) activated carboxylic acids [83][84][85][86][87][88][89], and anhydrides [90] enables the synthesis of homocysteine-γ-thiolactone derivatives. A carbamate linkage is formed by treatment with chloroformates [91].…”