Activity‐Based Protein Profiling – Celebrating the Groundbreaking Contributions of Benjamin Cravatt

We are excited to introduce the special issue of Israel Journal Chemistry dedicated awarding Wolf Prize in 2022 Benjamin Cravatt for his “contributions understanding chemistry cellular communication and inventing chemical methodologies study role carbohydrates, lipids, proteins such biological processes”. To celebrate Ben's countless achievements, we have invited several previous trainees, collaborators colleagues contribute this issue. With a focus on “Activity-based protein profiling”, collection is designed highlight widespread impact innovative chemoproteomic tools within chemistry, biology pharmaceutical science. Activity-based profiling (ABPP) method global analysis function protein-ligand interactions native systems that was pioneered by groups Ben Matt Bogyo around turn millennium.1, 2 This issue, which aims many different developments research field, begins with perspective himself, providing an insightful personal account past current applications future directions field ABPP (B. F. Cravatt, https://doi.org/10.1002/ijch.202300029). The article Howard Hang, colleague at Scripps Research, provides additional achievements sustained continuous community (H. C. https://doi.org/10.1002/ijch.202200066). continues two broad review articles give overview facets activity-based profiling. In context, Vinogradova coworkers tools, translational potential technologies studying states (K. A. Scott, T. L. Zhang, S. Y. Xi, B. Ngo, E. V. Vinogradova, https://doi.org/10.1002/ijch.202200101). Besides being able activity globally, it also highly desirable elucidate effects based locations cell. Therefore, Moellering discussion application these illuminate spatial regulation activities cells (C. Swenson, K. Smitha Pillai, J. Carlos, R. Moellering, https://doi.org/10.1002/ijch.202200104). further sections, focusses enabled ABPP. Early were largely focused development fluorophosphonate (FP)-based related probes characterizing serine hydrolase enzyme family. area be very active fruitful Adibekian highlights recent specific reactive used their Racioppo, N. Qiu, Adibekian, https://doi.org/10.1002/ijch.202300016). Furthermore, Birner-Gruenberger gives detailed insights into lipid hydrolases (S. Honeder, Tomin, M. Schinagl, Pfleger, Hoehlschen, Darnhofer, Schittmayer, Birner-Gruenberger, https://doi.org/10.1002/ijch.202200078). van der Stelt coworkers, use our endocannabinoid system develop compounds modulate highlighted (N. Zhu, P. Janssen, Stelt, https://doi.org/10.1002/ijch.202200115). Demonstrating diverse profiling, Pezacki provide FP microRNA during viral infection (P. Evers, Pezacki, https://doi.org/10.1002/ijch.202200088). reviews nicely complemented articles. first Verhelst describes synthesis FP-alkyne probe its elaboration dual color labeling (J. Yang, D. Korovesis, Ji, Kahler, Vanhoutte, H. Verhelst, https://doi.org/10.1002/ijch.202200094). second Bachovchin elucidation substrate scope proteases DPP8/9 directly lysate human (A. Bhattacharjee, Bachovchin, https://doi.org/10.1002/ijch.202200117). demonstration utility family spurred array families. Breinbauer generation investigate oxidases reductases can target families as exemplified functional converted electrophiles oxidation (L. Krammer, Breinbauer, https://doi.org/10.1002/ijch.202200086). Huang focuses glycan-binding -processing well glycosylated (Z. Vilen, Reeves, Huang, https://doi.org/10.1002/ijch.202200097). Traditional rely bind defined More work utilizes reactivity-based where grouped not class, but presence nucleophilic amino acids – concept group isoTOP-ABPP platform.3, 4 Reactivity-based has been widely utilized cysteine-mediated Wang quantitative chemoproteomics context (W. Xiao, Chen, Wang, https://doi.org/10.1002/ijch.202200100). These lately expanded other beyond cysteine (for see e. g.5). As example, Hsu methods tyrosines proteome W. Brulet, Ciancone, Yuan, K.-L. Hsu, https://doi.org/10.1002/ijch.202300001). One important ability screen inhibitors proteome, thereby concurrently evaluating inhibitor potency selectivity. studies routinely identify multitude new ligandable binding sites amenable covalent ligands.4 Several summarize outlooks ligand discovery. Parker insight fragment-based discovery using affinity- (I. Forrest, G. Parker, https://doi.org/10.1002/ijch.202200098). Additionally, Zhang case including traditional target-focused against complex Ekanayake, https://doi.org/10.1002/ijch.202200105). Marto explicitly power competitive some exciting facilitated Sharafi, Pin Teh, Bratt, Buhrlage, Marto, https://doi.org/10.1002/ijch.202200113). While modify and, thereby, inhibit function, method, known ligand-directed directed ligands generate traceless modification without inhibiting protein's function. discussed Hamachi chemistries Sakamoto, I. Hamachi, https://doi.org/10.1002/ijch.202200077). round up section, paper library cyclic peptides bearing fluorosulfate-based warheads exploration targets proteomes (F. Faucher, Abegg, Ipock, Lovell, Bogyo, https://doi.org/10.1002/ijch.202300020). broadly dysregulated numerous disease states. prokaryotic bacterial infections. Hatzios post-translational modifications host (R. Ramanathan, Hatzios, https://doi.org/10.1002/ijch.202200095). Chang allow functions physiology, pathogenesis metabolism Malarney, Chang, https://doi.org/10.1002/ijch.202200076). Wright discusses characterize bacteria host-associated environmental microbiomes Wright, Hudson, Garcia, https://doi.org/10.1002/ijch.202200099). Together, contributions serves discovering developing pharmacological tools. academic excellence, nature additionally biotech companies he advised founded. reach science undeniable, reaches own achievements. tremendous mentor younger scientists throughout career. His immense training inspiring underscored myriads alumni from lab now holding leading roles both academia industry. boundless energy contagious enthusiasm always inspired us will continue inspire future. honor deserving recognition through hope celebrating award snapshot everything accomplished glimpse promising yet come. Data sharing applicable no data created or analyzed study.