Fluorine‐18 labeling of peptide nucleic acids

Abstract

SummaryPeptide nucleic acids (PNAs) are a unique class of synthetic macromolecules, originally designed as ligands for the recognition of double stranded DNA. From a chemical point of view, the deoxyribose phosphate backbone of DNA is replaced by a pseudo-peptide N-(2-aminoethyl)glycyl backbone, while the nucleobases of DNA (adenine, guanine, cytosine and thymine) are retained. Due to the increasing interest in the labeling of peptide nucleic acids (PNAs) as potent diagnostic agents in nuclear medicine, we have used and adapted the reliable methodology developed for the fluorine-18 labeling of oligonucleotides and have now demonstrated that it is possible to label PNAs in sufficient quantity and with high specific radioactivity for PET studies in a time compatible with the half life of fluorine-18.

Improved Large‐Scale Liquid‐Phase Synthesis and High‐Temperature NMR Characterization of Short ­(F‐)PNAs

“…Yet, this method has not been utilized for analyzing PNA, a DNA or RNA mimic based on a non-charged, achiral, and pseudopeptidic backbone consisting of N-(2-aminoethyl)glycine (Aeg; 1) units [11]. Moreover, there are only five reports on fluorine modified PNA: i) a multistep synthesis of (2,4-difluoro-5-methylphenyl)acetic acid (2) and its Boc-protected monomer [12], ii) a hybridization survey of PNA containing fluoroaromatic residues [13], iii) two studies on synthesis and hybridization of fluorinated olefinic PNA [14] [15], and iv) one on 18 F labeling [16]. PNA is reasoned as a model structure for a primordial genetic material [17 -23] and was recently used in the design of protocells [24 -27] that are not based on chemistry occurring in todays biosphere.…”

Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the 18F labeling of bioactive peptides

“…16 Among the successful radiobioconjugations reported, the synthesis of bifunctional molecules 2-bromo-N-3-(2-[ 18 17 later it was used to prepare 18 F-modified Spiegelmers, 18,19 short interfering RNA, 20 and polyamide nucleic acids. 21,22 [ 18 F]FPyME was used to successfully label variety of thiol-containing peptides and proteins. 23 We sought to employ a 2-substituted pyridine [ 18 F]fluorination in the preparation of a general labeling agent for use with biomolecules of interest to PET.…”

Fluorine‐18 labelling of PNAs functionalized at their pseudo‐peptidic backbone for imaging studies with PET

“…17,18 It has so far been used once for the labelling of a selected PNA with fluorine-18. 19 Several groups have prepared radiometal-labelled PNAs or fluorescent chimerical PNA-peptide conjugates. 9,10 The strategies employed use all chemical properties of the pseudopeptidic backbone allowing the functionalization of the C-and N-terminus end, as well as internal amino-acid-C-a functionalization by introduction of non-glycine residues or reactive linkers.…”

“…18 F]fluorobenzyl)-2-bromoacetamide reagent based on previously developed methodology 19 and report that this strategy can routinely and efficiently be applied to the labelling of this particular class of oligonucleotide-like macromolecules. Thirteen PNAs, of the same sequence but presenting selected modifications of the pseudo-peptidic backbone were labelled with fluorine-18 ([ …”