Synthesis and application of photoproline - a photoactivatable derivative of proline

Abstract

A convenient synthesis is described of a derivative of L-proline called photoproline, containing a diazirine group at position-4 of the pyrrolidine ring, starting from L-4-hydroxyproline. The use of Fmoc-L-photoproline in the synthesis of a cyclic peptidomimetic antibiotic demonstrates that this photoprobe can be incorporated into synthetic peptides using solid-phase Fmoc chemistry. Photoproline may be of wide value in the preparation of diverse peptide-based photoaffinity probes.

New Trends in Diaziridine Formation and Transformation (a Review)

“…The synthesis of spirocyclic 3H-diazirine-containing building blocks has been discussed in the literature to a lesser extent [36]; however, it can potentially be employed to probe underexplored parts of proteome with libraries derived from structurally similar scaffolds of the parent's analogues [13,14,37]. Currently, spirocyclic 3H-diazirines can be found in steroid [38][39][40], proline [41,42], the simplified structure of chamuvarinin [43] analogues, and 1,5-disubsituted tetrazoles containing 3H-diazirine [44]. In a process with fewer steps, the crude diaziridine formed using the conventional method can be used directly for the synthesis of functionalized spirocyclic 3H-diazirine without using the chromatographic technique [36].…”

Photolabeling Strategies to Study Membranotropic Peptides Interacting with Lipids and Proteins in Membranes

“…Photoaffinity labeling experiments were performed to determine whether L27–11 binds to LptD in intact cells ( PA PAO1 WT ) . For this task, a photoreactive analogue of L27–11 , PAL-1 , was synthesized. , …”

“…These derivatives are extremely close to the natural amino acids, in terms of chemical structure and properties. Incorporation of these photoreactive amino acids had no impact on the antimicrobial properties of the different peptidomimetic probes. − , On the other hand, alkyldiazirine labels tend to be less stable and generate less reactive carbenes than aryldiazirines …”

“…49 For this task, a photoreactive analogue of L27−11, PAL-1, was synthesized. 49,54 PAL-1 contains a L-4,4-diazarinylproline (L-photoPro 14 ) and a biotin tag at position 1 (Figure 6B). Photoaffinity labeling of PA PAO1 WT cells with PAL-1 consistently revealed a major photolabeled protein by SDS-PAGE with an apparent mass close to that expected for PA LptD.…”

“…Incorporation of these photoreactive amino acids had no impact on the antimicrobial properties of the different peptidomimetic probes. [48][49][50][51]54 On the other hand, alkyldiazirine labels tend to be less stable and generate less reactive carbenes than aryldiazirines. 55 ■ CONCLUSION Affinity photo-cross-linking is a powerful and unique method to study the noncovalent interactions between membraneactive peptides and membrane components, as illustrated by the various examples detailed herein and between interacting partners in general.…”