Ian Seiple, PhD

Associate Professor
Executive Committee Member
Cardiovascular Research Institute
Seiple
[email protected]
Phone: +1 415 502-3623
555 Mission Bay Blvd South, Rm 452F
UCSF Box 3122
San Francisco, CA 94158
United States

Links

The Seiple Lab UCSF Profiles

Affiliations

Joint appointments

Department of Pharmaceutical Chemistry

What I do

Our research focuses on the application of modern chemical synthesis to biological challenges. Primary branches include complex molecule synthesis, reaction development, and de novo molecular design. Each project is chosen based on its fundamental scientific merit and its potential for immediate application. By design, our research provides opportunities for substantive collaboration with colleagues in adjacent fields, enabled by the interdisciplinary environment at University of California, San Francisco.

Departmental research area

chemical biology and medicinal chemistry

My research expertise

complex molecule synthesis, antibiotics, microbial resistance, medicinal chemistry, bioorthogonal chemistry, chemical methodology development

Professional background

Degrees

PhD, The Scripps Research Institute, 2011
Bachelor of Science, Chemistry, University of California, Berkeley, 2006

Research keywords

  • Spiro Compounds
  • Alkaloids
  • chemistry
  • Streptogramin Group A
  • Anti-Bacterial Agents
  • Bacillus subtilis
  • Authorship
  • Siderophores
  • Biotin
  • Serial Publications
  • Macrolides
  • Molecular Structure
  • Guanidines
  • Pyrroles
  • Micrococcus

Publications

Yang H, Zingaro VA, Lincoff J, Tom H, Oikawa S, Oses-Prieto JA, Edmondson Q, Seiple I, Shah H, Kajimura S, Burlingame AL, Grabe M, Ruggero D. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature. 2024 Aug 14.
Díaz RE, Ecker AK, Correy GJ, Asthana P, Young ID, Faust B, Thompson MC, Seiple IB, Van Dyken S, Locksley RM, Fraser JS. Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase. Elife. 2024 Jun 17; 12.
Díaz RE, Ecker AK, Correy GJ, Asthana P, Young ID, Faust B, Thompson MC, Seiple IB, Van Dyken SJ, Locksley RM, Fraser JS. Structural characterization of ligand binding and pH-specific enzymatic activity of mouse Acidic Mammalian Chitinase. bioRxiv. 2024 Mar 25.
Tolani B, Celli A, Yao Y, Tan YZ, Fetter R, Liem CR, de Smith AJ, Vasanthakumar T, Bisignano P, Cotton AD, Seiple IB, Rubinstein JL, Jost M, Weissman JS. Ras-mutant cancers are sensitive to small molecule inhibition of V-type ATPases in mice. Nat Biotechnol. 2022 12; 40(12):1834-1844.
Gramespacher JA, Cotton AD, Burroughs PWW, Seiple IB, Wells JA. Roadmap for Optimizing and Broadening Antibody-Based PROTACs for Degradation of Cell Surface Proteins. ACS Chem Biol. 2022 05 20; 17(5):1259-1268.
Prasad NK, Seiple IB, Cirz RT, Rosenberg OS. Leaks in the Pipeline: a Failure Analysis of Gram-Negative Antibiotic Development from 2010 to 2020. Antimicrob Agents Chemother. 2022 05 17; 66(5):e0005422.
Cotton AD, Seiple IB. Examining Gender Imbalance in Chemistry Authorship. ACS Chem Biol. 2021 11 19; 16(11):2042-2046.
Cotton AD, Wells JA, Seiple IB. Biotin as a Reactive Handle to Selectively Label Proteins and DNA with Small Molecules. ACS Chem Biol. 2022 12 16; 17(12):3270-3275.
Shi X, Li Q, Dai Z, Tran AA, Feng S, Ramirez AD, Lin Z, Wang X, Chow TT, Chen J, Kumar D, McColloch AR, Reiter JF, Huang EJ, Seiple IB, Huang B. Label-retention expansion microscopy. J Cell Biol. 2021 09 06; 220(9).
Zhao X, Garcia JQ, Tong K, Chen X, Yang B, Li Q, Dai Z, Shi X, Seiple IB, Huang B, Guo S. Polarized endosome dynamics engage cytoplasmic Par-3 that recruits dynein during asymmetric cell division. Sci Adv. 2021 06; 7(24).
Cai L, Seiple IB, Li Q. Modular Chemical Synthesis of Streptogramin and Lankacidin Antibiotics. Acc Chem Res. 2021 04 20; 54(8):1891-1908.
Cotton AD, Nguyen DP, Gramespacher JA, Seiple IB, Wells JA. Development of Antibody-Based PROTACs for the Degradation of the Cell-Surface Immune Checkpoint Protein PD-L1. J Am Chem Soc. 2021 01 20; 143(2):593-598.
Boyce JH, Dang B, Ary B, Edmondson Q, Craik CS, DeGrado WF, Seiple IB. Platform to Discover Protease-Activated Antibiotics and Application to Siderophore-Antibiotic Conjugates. J Am Chem Soc. 2020 12 23; 142(51):21310-21321.
Li Q, Seiple IB. Modular synthesis of streptogramin antibiotics. Synlett. 2021 Apr; 32(7):647-654.
Sundaram A, Chen C, Isik Reed N, Liu S, Ki Yeon S, McIntosh J, Tang YZ, Yang H, Adler M, Beresis R, Seiple IB, Sheppard D, DeGrado WF, Jo H. Dual antagonists of α5β1/αvβ1 integrin for airway hyperresponsiveness. Bioorg Med Chem Lett. 2020 11 15; 30(22):127578.
Li Q, Pellegrino J, Lee DJ, Tran AA, Chaires HA, Wang R, Park JE, Ji K, Chow D, Zhang N, Brilot AF, Biel JT, van Zundert G, Borrelli K, Shinabarger D, Wolfe C, Murray B, Jacobson MP, Mühle E, Chesneau O, Fraser JS, Seiple IB. Synthetic group A streptogramin antibiotics that overcome Vat resistance. Nature. 2020 10; 586(7827):145-150.
Cai L, Yao Y, Yeon SK, Seiple IB. Modular Approaches to Lankacidin Antibiotics. J Am Chem Soc. 2020 09 02; 142(35):15116-15126.
Liu J, Cai L, Sun W, Cheng R, Wang N, Jin L, Rozovsky S, Seiple IB, Wang L. Photocaged Quinone Methide Crosslinkers for Light-Controlled Chemical Crosslinking of Protein-Protein and Protein-DNA Complexes. Angew Chem Int Ed Engl. 2019 12 19; 58(52):18839-18843.
Li Q, Seiple IB. A concise route to virginiamycin M2. Tetrahedron. 2019 Jun 14; 75(24):3309-3318.
Yao Y, Cai L, Seiple IB. Synthesis, Structural Reassignment, and Antibacterial Evaluation of 2,18-Seco-Lankacidinol B. Angew Chem Int Ed Engl. 2018 10 08; 57(41):13551-13554.
Li Q, Seiple IB. Modular, Scalable Synthesis of Group A Streptogramin Antibiotics. J Am Chem Soc. 2017 09 27; 139(38):13304-13307.
Seiple IB, Zhang Z, Jakubec P, Langlois-Mercier A, Wright PM, Hog DT, Yabu K, Allu SR, Fukuzaki T, Carlsen PN, Kitamura Y, Zhou X, Condakes ML, Szczypinski FT, Green WD, Myers AG. A platform for the discovery of new macrolide antibiotics. Nature. 2016 05 19; 533(7603):338-45.
Seiple, I. B.; Hog, D. T.; Myers, A. G.. Practical Protocols for the Preparation of Highly Enantioenriched Silyl Ethers of (R)-3-Hydroxybutan-2-one, Building Blocks for the Synthesis of Macrolide Antibiotics. Synlett. 2015; 1(27):57-60.
Wright PM, Seiple IB, Myers AG. The evolving role of chemical synthesis in antibacterial drug discovery. Angew Chem Int Ed Engl. 2014 Aug 18; 53(34):8840-69.
Seiple IB, Mercer JA, Sussman RJ, Zhang Z, Myers AG. Stereocontrolled synthesis of syn-β-Hydroxy-α-amino acids by direct aldolization of pseudoephenamine glycinamide. Angew Chem Int Ed Engl. 2014 Apr 25; 53(18):4642-7.
Lansdell TA, Hewlett NM, Skoumbourdis AP, Fodor MD, Seiple IB, Su S, Baran PS, Feldman KS, Tepe JJ. Palau'amine and related oroidin alkaloids dibromophakellin and dibromophakellstatin inhibit the human 20S proteasome. J Nat Prod. 2012 May 25; 75(5):980-5.
Köck M, Schmidt G, Seiple IB, Baran PS. Configurational analysis of tetracyclic dimeric pyrrole-imidazole alkaloids using a floating chirality approach. J Nat Prod. 2012 Feb 24; 75(2):127-30.
Seiple IB, Su S, Young IS, Nakamura A, Yamaguchi J, Jørgensen L, Rodriguez RA, O'Malley DP, Gaich T, Köck M, Baran PS. Enantioselective total syntheses of (-)-palau'amine, (-)-axinellamines, and (-)-massadines. J Am Chem Soc. 2011 Sep 21; 133(37):14710-26.
Ji Y, Brueckl T, Baxter RD, Fujiwara Y, Seiple IB, Su S, Blackmond DG, Baran PS. Innate C-H trifluoromethylation of heterocycles. Proc Natl Acad Sci U S A. 2011 Aug 30; 108(35):14411-5.
Fujiwara Y, Domingo V, Seiple IB, Gianatassio R, Del Bel M, Baran PS. Practical C-H functionalization of quinones with boronic acids. J Am Chem Soc. 2011 Mar 16; 133(10):3292-5.
Seiple IB, Su S, Rodriguez RA, Gianatassio R, Fujiwara Y, Sobel AL, Baran PS. Direct C-H arylation of electron-deficient heterocycles with arylboronic acids. J Am Chem Soc. 2010 Sep 29; 132(38):13194-6.
Seiple IB, Su S, Young IS, Lewis CA, Yamaguchi J, Baran PS. Total synthesis of palau'amine. Angew Chem Int Ed Engl. 2010 Feb 01; 49(6):1095-8.
Su S, Seiple IB, Young IS, Baran PS. Total syntheses of (+/-)-massadine and massadine chloride. J Am Chem Soc. 2008 Dec 10; 130(49):16490-1.
Yamaguchi J, Seiple IB, Young IS, O'Malley DP, Maue M, Baran PS. Synthesis of 1,9-dideoxy-pre-axinellamine. Angew Chem Int Ed Engl. 2008; 47(19):3578-80.
O'Malley DP, Yamaguchi J, Young IS, Seiple IB, Baran PS. Total synthesis of (+/-)-axinellamines A and B. Angew Chem Int Ed Engl. 2008; 47(19):3581-3.
Köck M, Grube A, Seiple IB, Baran PS. The pursuit of palau'amine. Angew Chem Int Ed Engl. 2007; 46(35):6586-94.
Liang G, Xu Y, Seiple IB, Trauner D. Synthesis of taiwaniaquinoids via Nazarov triflation. J Am Chem Soc. 2006 Aug 30; 128(34):11022-3.
Liang G, Seiple IB, Trauner D. Stereoselective syntheses of the bioactive polypropionates aureothin, N-acetylaureothamine, and aureonitrile. Org Lett. 2005 Jul 07; 7(14):2837-9.