PUBLICATIONS

SL. Mixed Amide Paracyclophane Assemblies Emulating Supramolecular Copolymers. Cole D. Stearns,† Ajeet Kumar,† Ion Ghiviriga, Lukasz M. Dobrzycki, Khalil A. Abboud, and Ronald K. Castellano*. J. Am. Chem. Soc. 2025, 147, 24615.

SL. Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets. Mary E. Law,† Zaafir M. Dulloo,† Brian Hardy, Ania Kelegama, Reagan Clark, Mariana Rivas Montbrun, Gabriella Antmann, Srihith Nooka, Ronald K. Castellano, and Brian K. Law*. Biomolecules 2025, 15, 1146.

SL. DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress. ME Law,† ZM. Dulloo,† SR Eggleston, GP Takacs, GM Alexandrow, Y il Lee, M Wang, B Hardy, H Su, B Forsyth, P Das, PK Datta, CW Chiang, A Sharma, SRR Kanumuri, OA Guryanova, JK Harrison, B Tirosh, RK Castellano*, and BK Law*. Mol. Cancer Res. (2025) 23 (7): 622.

SL. Beta-cyclodextrin formulation of a disulfide-bond disrupting agent for improved systemic exposure. Zaafir M. Dulloo, Ion Ghiviriga, Mary E. Law, Sarvesh K. Verma, Abhisheak Sharma, Brian K. Law*, and Ronald K. Castellano*. RSC Med. Chem. 2025, 16, 3622.

SL. Diagnosing the role of hydrogen bonding in the organization, aggregation, and optical properties of phthalhydrazide-functionalized molecules in solution and solid state. Cheng-Yen Pan,† Nathan J. Grinalds,† Ion Ghiviriga, Khalil A. Abboud, Jiangeng Xue*, and Ronald K. Castellano*. New J. Chem. 2025, 49, 5330.

SL. 2-(1,1-Dicyanomethylene)rhodanine-Functionalized Oligothiophenes: A Structure–Property Investigation of Z/E Photoisomerization Behavior. Cory T. Kornman,† Parag Das,† Lei Li, Asmerom O. Weldeab, Ion Ghiviriga, and Ronald K. Castellano*. J. Org. Chem. 2024, 89, 13853.

SL. Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives. Tural N. Akhmedov, Ajeet Kumar, Daken J. Starkenburg, Kyle J. Chesney, Khalil A. Abboud, Novruz G. Akhmedov, Jiangeng Xue, and Ronald K. Castellano*. Beilstein J. Org. Chem. 2024, 20, 1037.

SL. Dicyanorhodanine-Pyrrole Conjugates for Visible Light-Driven Quantitative Photoswitching in Solution and the Solid State. Parag Das, Nathan J. Grinalds, Ion Ghiviriga, Khalil A. Abboud, Łukasz Dobrzycki, Jiangeng Xue*, and Ronald K. Castellano*. J. Am. Chem. Soc. 2024, 146, 11932.

SL. A small molecule multi-FRET platform from benzotrifuranone. Ashton N. Bartley , Sadie F. DePeter, and Ronald K. Castellano*. Dyes and Pigments 220 (2023) 111732.

SL. Enlightening the Well-Controlled Photochemical Behavior of 1,1-Dicyanomethylene-3-Indanone-Functionalized π-Conjugated Molecules. Parag Das, Cory T. Kornman, Ion Ghiviriga, Khalil A. Abboud, and Ronald K. Castellano*. Chem. Mater. 2023, 35, 8122.

SL. Thin-Film Morphology and Optical Properties of Photoisomerizable Donor−Acceptor Oligothiophenes. David M. Camero, Nathan J. Grinalds, Cory T. Kornman, Stefano Barba, Lei Li, Asmerom O. Weldeab, Ronald K. Castellano,* and Jiangeng Xue*. ACS Appl. Mater. Interfaces 2023, 15, 25134.

SL. Inhibitors of ERp44, PDIA1, and AGR2 induce disulfide-mediated oligomerization of Death Receptors 4 and 5 and cancer cell death. Mary E Law, Elham Yaaghubi, Amanda F Ghilardi, Bradley J Davis, Renan B Ferreira, Jin Koh, Sixue Chen, Sadie F DePeter, Christopher M Schilson, Chi-Wu Chiang, Coy D Heldermon, Peter Nørgaard, Ronald K Castellano*, and Brian K Law*. Cancer Letters 534 (2022) 215604.

SL. Repurposing Tranexamic Acid as an Anticancer Agent. Mary E. Law, Bradley J. Davis, Amanda F. Ghilardi, Elham Yaaghubi, Zaafir M. Dulloo, Mengxiong Wang, Olga A. Guryanova, Coy D. Heldermon, Stephan C. Jahn, Ronald K. Castellano, and Brian K. Law*. Front. Pharmacol. 2022, 12, 792600.

SL. Anticancer
Agents Derived from Cyclic Thiosulfonates: Structure-Reactivity and Structure-Activity Relationships. Amanda F. Ghilardi,† Elham Yaaghubi,† Renan B. Ferreira, Mary E. Law, Yinuo Yang, Bradley J. Davis, Christopher M. Schilson, Ion Ghiviriga, Adrian E. Roitberg, Brian K. Law*, and Ronald K. Castellano*. ChemMedChem 2022, 17, e202200165.

SL. Tuning Supramolecular Polymer Assembly through Stereoelectronic Interactions. Will R. Henderson, Guancen Liu, Khalil A. Abboud, and Ronald K. Castellano*. J. Am. Chem. Soc. 2021, 143, 12688.

SL. Structure–Assembly–Property Relationships of Simple Ditopic Hydrogen-Bonding-Capable π-Conjugated Oligomers. Asmerom O. Weldeab , Cory T. Kornman , Lei Li , Daken J. Starkenburg, Xueying Zhao, Danielle E. Fagnani , Sara J. Sadovy, Scott S. Perry, Jiangeng Xue *, Ronald K. Castellano*. Organic Materials 2021, 3, 390.

SL. Supramolecular polymerization of chiral molecules devoid of chiral centers. Will R Henderson, and Ronald K Castellano*. Polym Int 2021; 70: 897.

SL. Influence of Amide Connectivity on the Hydrogen-Bond-Directed Self-Assembly of [n.n]Paracyclophanes. Will R. Henderson, Ajeet Kumar, Khalil A. Abboud, and Ronald K. Castellano*. Chem. Eur. J. 2020, 26, 17588.

SL. Photoisomerization of dicyanorhodanine-functionalized thiophenes. Cory T. Kornman,† Lei Li,† Asmerom O. Weldeab, Ion Ghiviriga, Khalil A. Abboud, and Ronald K. Castellano *. Chem. Sci. 2020, 11, 10190.

SL. Self-Assembling [n.n]Paracyclophanes: A Structure–Property Relationship Study. Will R. Henderson, Yu Zhu, Danielle E. Fagnani, Guancen Liu, Khalil A. Abboud, and Ronald K. Castellano*. J. Org. Chem. 2020, 85, 1158.

SL. Disulfide bond-disrupting agents activate the tumor necrosis family-related apoptosis-inducing ligand/death receptor 5 pathway. Mengxiong Wang, Mary E. Law, Bradley J. Davis, Elham Yaaghubi, Amanda F. Ghilardi, Renan B. Ferreira, Chi-Wu Chiang, Olga A. Guryanova, Daniel Kopinke, Coy D. Heldermon, Ronald K. Castellano*, and Brian K. Law*. Cell Death Discovery 2019, 5, 153.

SL. A metabolic switch in proteasome inhibitor-resistant multiple myeloma ensures higher mitochondrial metabolism, protein folding and sphingomyelin synthesis. Lenka Besse,† Andrej Besse,† Max Mendez-Lopez, Katerina Vasickova, Miroslava Sedlackova, Petr Vanhara, Marianne Kraus, Jürgen Bader ,Renan B. Ferreira, Ronald K. Castellano, Brian K. Law, and Christoph Driessen*. Haematologica 2019, 104, e415.

SL. A novel proteotoxic combination therapy for EGFR+ and HER2+ cancers. Mengxiong Wang, Renan B. Ferreira, Mary E. Law, Bradley J. Davis, Elham Yaaghubi, Amanda F. Ghilardi, Abhisheak Sharma, Bonnie A. Avery, Edgardo Rodriguez, Chi-Wu Chiang, Satya Narayan, Coy D. Heldermon, Ronald K. Castellano*, and Brian K. Law*. Oncogene 2019, 38, 4264.

SL. Transannular Hydrogen Bonding in Planar‐Chiral [2.2] Paracyclophane‐Bisamides. Will R. Henderson, Danielle E. Fagnani, Jonathan Grolms, Khalil A. Abboud, Ronald K. Castellano*. Helv. Chim. Acta 2019, 102, e1900047.

SL. Differentiating the mechanism of self-assembly in supramolecular polymers through computation. Divya B. Korlepara, Will R. Henderson, Ronald K. Castellano, and Sundaram Balasubramanian*. Chem. Commun. 2019, 55, 3773.

SL. Synthesis, Optoelectronic Properties, Self-Association, and Base Pairing of Nucleobase-Functionalized Oligothiophenes. Danielle E. Fagnani, Raghida Bou Zerdan, and Ronald K. Castellano*. J. Org. Chem. 2018, 83, 12711.

SL. The unfolded protein response as a target for anticancer therapeutics. Mengxiong Wang, Mary E Law, Ronald K Castellano, Brian K Law*. Critical Reviews in Oncology/Hematology 127 (2018) 66.

SL. Pyridine-terminated low gap π-conjugated oligomers: design, synthesis, and photophysical response to protonation and metalation. Asmerom O. Weldeab, Lei Li, Seda Cekli, Khalil A. Abboud, Kirk S. Schanze, and Ronald K. Castellano*. Org. Chem. Front. 2018, 5, 3170.

SL. Tuning the structural and spectroscopic properties of donor–acceptor–donor oligomers via mutual X-bonding, H-bonding, and pi–pi interactions. Asmerom O. Weldeab, April Steen, Daken J. Starkenburg, Jon Steven Dal Williams, Khalil A. Abboud, Jiangeng Xue, Nathan I. Hammer, Ronald K. Castellano*, and Davita L. Watkins*. J. Mater. Chem. C 2018, 6, 11992.

SL. Disulfide bond disrupting agents activate the unfolded protein response in EGFR- and HER2-positive breast tumor cells. Renan B. Ferreira, Mengxiong Wang, Mary E. Law, Bradley J. Davis, Ashton N. Bartley, Paul J. Higgins, Michael S. Kilberg, Katherine E. Santostefano, Naohiro Terada, Coy D. Heldermon, Ronald K. Castellano, and Brian K. Law*. Oncotarget 2017, 8, 28971.

38. Rudolf, J. D.;* Chang, C.-Y. Terpene synthases in disguise: enzymology, structure, and opportunities of non-canonical terpene synthases. Nat. Prod. Rep. 2020, 37, 425–463.

56. Fluegel, L. L.; Deng, M.-R.; Su, P.; Kalkreuter, E.; Yang, D.; Rudolf, J. D.; Dong, L.-B.; Shen, B.* Development of platensimycin, platencin, and platensilin overproducers by biosynthetic pathway engineering and fermentation medium optimization. J. Ind. Microbiol. Biotechnology. 2024, 51, kuae003.

39. Zhang, X.; King-Smith, E.; Dong, L.-B.; Yang, L.-C.; Rudolf, J. D.; Shen, B.; Renata, H.* Divergent synthesis of complex diterpenes through a hybrid oxidative approach. Science 2020, 369, 799–806.

37. Dong, L.-B.; Liu, Y.-C.; Cepeda, A.; Kalkreuter, E.; Deng, M.-R.; Rudolf, J. D.; Chang, C.; Joachimiak, A.; Phillips Jr., G. N.;  Shen, B.* Characterization and crystal structure of a nonheme diiron monooxygenase involved in platensimycin and platencin biosynthesis. J. Am. Chem. Soc. 2019, 141, 12406–12412.

36. Su, M.; Qiu, L.; Deng, Y.; Ruiz, C. H.; Rudolf, J. D.; Dong, L.-B.; Feng, X.; Cameron, M. D.; Shen, B.; Duan, Y.; Huang, Y.* Evaluation of platensimycin and platensimycin-inspired thioether analogues against methicillin-resistant Staphylococcus aureus in topical and systemic infection mouse models. Mol. Pharm. 2019, 16, 3065–3071.

35. Dong, L.-B.; Zhang, X.; Rudolf, J. D.; Deng, M.-R.; Kalkreuter, E.; Cepeda, A. J.; Renata, H.; Shen, B.* Cryptic and stereospecific hydroxylation, oxidation, and reduction in platensimycin and platencin biosynthesis. J. Am. Chem. Soc. 2019, 141, 4043–4050.

34. Rudolf, J. D.; Dong, L.-B.; Zhang, X.; Renata, H.; Shen, B.* Cytochrome P450-catalyzed hydroxylation initiating ether formation in platensimycin biosynthesis. J. Am. Chem. Soc. 2018, 140, 12349–12353.

33. Annaval, T.; Han, L.; Rudolf, J. D.; Xie G.; Yang, D.; Chang, C.-Y.; Ma, M.; Crnovcic, I.; Miller, M. D.; Soman, J.; Xu, W.; Phillips Jr., G. N.; Shen, B.* Biochemical and structural characterization of TtnD, a prenylated FMN-dependent decarboxylase from the tautomycetin biosynthetic pathway. ACS Chem. Biol. 2018, 13, 2728–2738.

32. Kwong, T.; Ma, M.; Pan, G.; Hindra; Yang, D.; Lohman, J. R..; Rudolf, J. D.; Cleveland, J. L.; Shen, B.* P450-catalyzed tailoring steps in leinamycin biosynthesis featuring regio- and stereoselectivity hydroxylations and substrate promiscuities. Biochemistry 2018, 57, 5005–5013.

31. Chang, C.-Y.; Yan, X.; Crnovcic, I.; Annaval, T.; Chang, C.; Nocek, B.; Rudolf, J. D.; Yang, D.; Hindra; Babnigg, G.; Joachimiak, A.; Phillips Jr., G. N.;  Shen, B.* Resistance to enediyne antitumor antibiotics by sequestration. Cell Chem. Biol. 2018, 25, 1075–1085.

30. Dong, L.-B.; Rudolf, J. D.; Deng, M.-R.; Yan, Y.;  Shen, B.* Discovery of the tiancilactone antibiotics by genome mining of atypical bacterial type II diterpene synthases. ChemBioChem 2018, 19, 1727–1733.

29. Dong, L.-B.; Rudolf, J. D.; Kang, D.; Wang, N.;  He, C. Q.; Deng, Y.; Huang, Y.; Houk, K. N.; Duan, Y.; Shen, B.* Biosynthesis of thiocarboxylic acid-containing natural products. Nat. Commun. 2018, 9, 2362.

28. Wang, N.; Rudolf, J. D.; Dong, L.-B.; Osipiuk, J.; Hatzos-Skintges, C.; Endres, M.; Chang, C.-Y.; Babnigg, G.; Joachimiak, A.; Phillips Jr., G. N.;  Shen, B.* Natural separation of the acyl-CoA ligase reaction results in a non-adenylating enzyme. Nat. Chem. Biol. 2018, 14, 730–737.

27. Chang, C.-Y.; Lohman, J. R.; Huang T.; Michalska, K.; Bigelow, L.; Rudolf, J. D.; Jedrzejczak, R.; Yan, Y.; Ma, M.; Babnigg, G.; Joachimiak, A.; Phillips Jr., G. N.;  Shen, B.* Structural insights into the free-standing condensation enzyme SgcC5 catalyzing ester-bond formation in the biosynthesis of the enediyne antitumor antibiotic C-1027. Biochemistry 2018, 57, 3278–3288.

26. Annaval, T.; Rudolf, J. D.; Chang, C.-Y.; Lohman, J. R.; Kim, Y.; Bigelow, L.; Jedrzejczak, R.; Babnigg, G.; Joachimiak, A.; Phillips Jr., G. N.;  Shen, B.* Crystal structure of the thioesterase SgcE10 supporting common polyene intermediates in 9- and 10-membered enediyne core biosynthesis. ACS Omega. 2017, 2, 5159–5169.

25. Rudolf, J. D.; Chang, C.-Y.; Ma, M.; Shen, B.* Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function. Nat. Prod. Rep. 2017, 34, 1141–1172.

24. Rudolf, J. D.; Crnovcic, I.; Shen, B.* The role of combinatorial biosynthesis in natural products discovery. In Chemical Biology of Natural Products. Newman, D.J.; Cragg, G.M.; Grothaus, P.G.; Eds. 2017, pp. 87–125.

23. Falzone, M.; Crespo, E.; Jones, K.; Khan, G.; Korn, V.; Patel, A.; Patel, M.; Patel, K.; Perkins, C.; Siddiqui, S.; Stenger, A.; Yu, E.; Gelber, M.; Scheffler, R.; Nayda, V.; Ravin, A.; Komal, R.; Rudolf, J. D.; Shen, B.; Gullo, V.; Demain, A.* Nutritional control of antibiotic production by Streptomyces platensis MA7327: importance of L-aspartic acid. J. Antibiot. 2017, 70, 828–831.

22. Rudolf, J. D.; Dong, L.-B.; Shen, B.* Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and medicine. Biochem. Pharm. 2017, 133, 139–151.

21. Ma, M.; Rateb, M. E.; Yang, D.; Rudolf, J. D.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; Shen, B.* Germicidins H–J from Streptomyces sp. CB00361. J. Antibiotic. 2017, 70, 200–203.

20. Dong, L.-B.; Rudolf, J. D.; Lin, L.; Ruiz, C.; Cameron, M .D.; Shen, B.* In vivo instability of platensimycin and platencin: Synthesis and biological evaluation of urea- and carbamate-platensimycin. Bioorg. Med. Chem. 2017, 25, 1990–1996.

19. Rudolf, J. D.; Dong, L.-B.; Manoogian, K.; Shen, B.* Biosynthetic origin of the ether ring in platensimycin. J. Am. Chem. Soc. 2016, 138, 16711–16721.

18. Yan, X.; Ge, H.; Huang, T.; Hindra; Yang, D.; Teng, Q.; Crnovcic, I.; Li, X.; Rudolf, J. D.; Lohman, J. R.; Gansemans, Y.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Van Nieuwerburgh, F.; Rader, C.; Duan, Y.; Shen, B.* Strain prioritization and genome mining for enediyne natural products. mBio 2016, 7, e02104-16.

17. Dong, L.-B.; Rudolf, J. D.; Shen, B.*  A mutasynthetic library of platensimycin and platencin analogues. Org. Lett. 2016, 18, 4606–4609.

16. Chang, C.-Y.; Lohman, J. R.; Cao, H.; Tan, K.; Rudolf, J. D.; Ma, M.; Xu, W.; Bingman, C. A.; Yennamalli, R. M.; Bigelow, L.; Babnigg, G.; Yan, X.; Joachimiak, A.; Phillips Jr., G.N.; Shen, B.*  Crystal structures of SgcE6 and SgcC, the two-component monooxygenase that catalyzes hydroxylation of a carrier protein-tethered substrate during the biosynthesis of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus. Biochemistry 2016, 55, 5142–5154.

15. Rudolf, J. D.; Dong, L.-B.; Cao, H.; Hatzos-Skintges, C.; Osipiuk, J.; Endres, M.; Chang, C.-Y.; Ma, M.; Babnigg, G.; Joachimiak, A.; Phillips Jr., G.N.; Shen, B.*  Structure of the ent-copalyl diphosphate synthase PtmT2 from Streptomyces platensis CB00739, a bacterial type II diterpene synthase. J. Am. Chem. Soc. 2016, 138, 10905–10915.

14. Huang, T.; Chang, C.-Y.; Lohman, J. R.; Rudolf, J. D.; Kim, Y.; Chang, C.; Yang, D.; Ma, M.; Yan, X.; Crnovcic, I.; Bigelow, L.; Clancy, S.; Bingman, C. A.; Yennamalli, R. M.; Babnigg, G.; Joachimiak, A.; Phillips Jr., G. N.; Shen, B.* Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027. J. Antibiot. 2016, 69, 731–740.

13. Dong, L.-B.; Rudolf, J. D.; Shen, B.* Antibacterial sulfur-containing platensimycin and platencin congeners from Streptomyces platensis SB12029. Bioorg. Med. Chem. 2016, 24, 6348–6353.

12. Rudolf, J. D.; Yan, X.; Shen, B.* Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery. J. Ind. Microbiol. Biotechnol. 2016, 43, 261–276.

11. Rudolf, J. D.; Bigelow, L.; Chang, C.; Cuff, M. E.; Lohman, J. R.; Chang, C.-Y.; Ma, M.; Yang, D.; Clancy, S.; Babnigg, G.; Joachimiak, A.; Phillips Jr., G. N.; Shen, B.* Crystal structure of the zorbamycin-binding protein ZbmA, the primary self-resistance element in Streptomycesflavoviridis ATCC21892. Biochemistry 2015, 54, 6842–6851.

10. Ma, M.; Rateb, M.; Teng, Q.; Yang, D.; Rudolf, J. D.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Li, X.; Rader, C.; Duan Y.; Shen, B.* Angucyclines and angucyclinones from Streptomyces sp. CB01913 featuring C-ring cleavage and expansion. J. Nat. Prod. 2015, 78, 2471–2780.

9. Rudolf, J. D.; Dong, L.-B.; Huang, T.; Shen, B.* A genetically amenable platensimycin- and platencin-overproducer as a platform for biosynthetic explorations: a showcase of PtmO4, a long-chain acyl-CoA dehydrogenase. Mol. BioSyst. 2015, 11, 2717–2726.

8. Shen, B.;* Hindra; Yan, X.; Huang, T.; Ge, H.; Yang, D.; Qihui, T.; Rudolf, J. D.; Lohman, J. R. Enediynes: Exploration of microbial genomics to discover new anticancer drug leads. Bioorg. Med. Chem. 2015, 25, 9–15.

7. Coughlin, J. M.; Rudolf, J. D.; Wang, L.; Galm, U.; Wendt-Pienkowski, E.; Tao, M.; Shen, B.* BlmB and TlmB provide resistance to the bleomycin family of antitumor antibiotics by N-acetylating metal-free bleomycin, tallysomycin, phleomycin, and zorbamycin. Biochemistry 2014, 53, 6901–6909.

6. Hindra; Huang, T.; Yang, D.; Rudolf, J. D.; Xie, P.; Xie, G.; Teng, Q.; Lohman, J. R.; Zhu, X.; Huang, Y.; Zhao, L.-X.; Jiang, Y.; Duan, Y.; Shen, B.* Strain prioritization for natural product discovery by a high-throughput real-time PCR method. J. Nat. Prod. 2014, 77, 2296–2303.

5. Ge, H.-M.; Huang, T.; Rudolf, J. D.; Lohman, J. R.; Huang, S.-X.; Guo, X.; Shen, B.* Enediyne polyketide synthases stereospecifically reduce the β-ketoacyl intermediates to β-D-hydroxyacyl intermediates in enediyne core biosynthesis. Org. Lett. 2014, 16, 3958–3961.

4. Xie, P.; Ma, M.; Rateb, M.; Shaaban, K.; Yu, Z.; Huang, S.-X.; Zhao, L.-X.; Zhu, X.; Yan, Y.; Peterson, R. M.; Lohman, J. R.; Yang, D.; Yin, M.; Rudolf, J. D.; Jiang, Y.; Duan, Y.; Shen, B.* Biosynthetic potential-based strain prioritization for natural product discovery – a showcase for diterpenoid producing actinomycetes. J. Nat. Prod. 2014, 77, 377–387.

3. Peterson, R. M.; Huang, T.; Rudolf, J. D.; Smanski, M. J.; Shen B.* Mechanisms of self-resistance in the platensimycin and platencin producing Streptomyces platensis MA7327 and MA7339 strains. Chem. Biol. 2014, 21, 389–397.