biostudies-literatureUnknown13(2)Han PPhotoaffinity labeling is a powerful technique to investigate the interactions between bioactive peptides and their targets. To construct a peptide-derived photoaffinity probe, at least two amino acids need to be modified or replaced, increasing experimental difficulties and negatively affecting activity. Herein, we report the synthesis of a clickable, photoreactive amino acid <i>p</i>-(4-(but-3-yn-1-yl)benzoyl)-l-phenylalanine (Abpa) and its Fmoc-protected version from 3-(4-bromophenyl)-1-propanol in 11 steps with an overall 12.5% yield. The amino acid contains both a photoreactive benzophenone and a clickable terminal alkyne which acts like a reporter tag by fast attachment to other functional groups <i>via</i> 'click' reaction, and a photoaffinity probe could be created by one single amRSC advances866-872https://www.ebi.ac.uk/biostudies/studies/S-EPMC9811243biostudies-literatureDesign and synthesis of a clickable, photoreactive amino acid <i>p</i>-(4-(but-3-yn-1-yl)benzoyl)-l-phenylalanine for peptide photoaffinity labeling.PMC9811243Han PLiu JJiang HWang FWan XBao SYao GfalseDesign and synthesis of a clickable, photoreactive amino acid <i>p</i>-(4-(but-3-yn-1-yl)benzoyl)-l-phenylalanine for peptide photoaffinity labeling.Photoaffinity labeling is a powerful technique to investigate the interactions between bioactive peptides and their targets. To construct a peptide-derived photoaffinity probe, at least two amino acids need to be modified or replaced, increasing experimental difficulties and negatively affecting activity. Herein, we report the synthesis of a clickable, photoreactive amino acid <i>p</i>-(4-(but-3-yn-1-yl)benzoyl)-l-phenylalanine (Abpa) and its Fmoc-protected version from 3-(4-bromophenyl)-1-propanol in 11 steps with an overall 12.5% yield. The amino acid contains both a photoreactive benzophenone and a clickable terminal alkyne which acts like a reporter tag by fast attachment to other functional groups <i>via</i> 'click' reaction, and a photoaffinity probe could be created by one single am2023-01-01T00:00:00Z2023 Jan2025-04-04T14:27:17.713Z2025-04-04T14:27:17.713ZS-EPMC98112433668691910.1039/d2ra07248c