High specific activity tritium labelling of biologically active small peptides and a related analogue

Abstract

Small peptides are often endowed with useful biological activity and two of these are L-leucyl-L-leucine methyl ester (1) and glycyl-L-glutamine (2). To advance research in this important area, they were tritiated at high specific activity. [ 3 H] L-Leucyl-L-leucine methyl ester (5) was prepared by the reaction of [ 3 H] L-leucine methyl ester (4) with BOC-Leu-OSu. [ 3 H] Glycyl-L-glutamine (7) was synthesized by the reaction of [ 3 H] L-glutamine with BOCGly-OSu. Biosynthesized from L-lysine and L-methionine, related small molecule L-propionylcarnitine taurinamide (3) was also tritiated, employing [ 3 H] taurine (10) and L-propionylcarnitine acid chloride (9).

Tritium NMR: A compilation of data and a practical guide

“…Five years ago, Filer published a review [88] dedicated to the synthesis and applications of the tritium-labeled [75] with the permission of Springer Nature alkaloids including indole alkaloids Reproduced with minor editing privilege from Vogt et al [83] with the permission of John Wiley and Sons enumeration of alkaloids is taken from the parent review). The author stated that "the extreme structural and functional variety of alkaloids has presented both valuable opportunities and complex synthetic challenges for their tritiation.…”

“…Egan and Filer [ 75 ] performed a high specific activity tritium labeling of biologically active small peptides illustrated here for L‐leucine and glycyl‐L‐glutamine in Figure 52. The spectrum of the benchmark tritiated L‐leucine (Figure 52, top) displayed a complex pattern of tritium installation into both the L‐leucine isopropyl methyls (1.0 ppm), as well as to the nearby methine and methylene positions (1.7 ppm).…”

“…Tritium proton decoupled NMR spectrum of [ 3 H] L‐leucine (top) and [ 3 H] glycyl‐L‐glutamine (bottom) recorded in D 2 O at 320 MHz. Reproduced with minor editing privilege from Egan and Filer [ 75 ] with the permission of Springer Nature…”

“…Reproduced with minor editing privilege from Ahern et al [69] with the permission of Springer Nature F I G U R E 4 7 Tritium proton decoupled NMR spectrum of [2-3 H] strychnine recorded in CDCl 3 at 320 MHz. Reproduced with minor editing privilege from Filer [70] with the permission of Springer Nature Egan and Filer [75] performed a high specific activity tritium labeling of biologically active small peptides illustrated here for L-leucine and glycyl-L-glutamine in Figure 52. The spectrum of the benchmark tritiated Lleucine (Figure 52, top) displayed a complex pattern of tritium installation into both the L-leucine isopropyl methyls (1.0 ppm), as well as to the nearby methine and methylene positions (1.7 ppm).…”

Radiolabelling small and biomolecules for tracking and monitoring

“…This is reported in the literature for smaller peptide sequences of only a few amino acids. 58 As an option for larger peptides, it is reported to incorporate the amino acid precursor into the sequence by solid phase synthesis. The most commonly used precursor amino acids are halogenated aromatic α-amino acids or synthetic-α-amino acids containing double or triple bonds.…”