195:
developed by
Ponders & Richards, Desjarlais & Handel, Dahiyat & Mayo. The folding kinetics of alpha3D are among the most extensively characterized of single-domain proteins, and it has been used as a template for design of metalloproteins. The company Arcellx used alpha3D as a starting point for design of chimeric antigen receptors (CARs). Clinical data announced in 2020 showed deep and durable responses of multiple myeloma, illustrating the potential of
30:
238:, which is in clinical trials for several indications. DeGrado's group also has contributed to the development of small molecule antagonists of integrins that reached clinical trials. His work on this subject with Dean Sheppard also formed the basis for founding Pliant Pharmaceuticals, a company conducting clinical trials on idiopathic pulmonary fibrosis (IPF) and primary sclerosing cholangitis.
194:
protein, which was biologically expressed, structurally validated, and whose sequence and structure were not based on the sequence or the precise tertiary structure of a natural protein. The sequence of alpha3D was designed using the computational sidechain repacking algorithms that had recently been
189:
protein design, a term they coined to describe the design of proteins from first principles rather than through modification of natural protein sequences. They pioneered parametric approaches to the design of water-soluble 4-helix (alpha4) and 3-helix bundles (alpha3D), and ion channel peptides. The
130:
Following high school graduation, DeGrado worked in a coat rack factory, an experience that motivated him to further his education. He attended colleges in the
Chicago suburbs, while running a lawn-mowing service. About this time, his father, Jim DeGrado, designed the highly successful Red Solo Cup,
225:
Because the original approaches to de novo protein design focused on physical chemical principles it was easily extended to design biologically active polymers and foldamers (short homogeneous, sequence-specific polymers that fold into unique structures). This work led to the design of
Brilacidin,
218:) DeGrado has also designed numerous proteins that mimic many of the catalytic and electron relay properties of heme and non-heme iron proteins, including a transmembrane protein capable of shuttling electrons across membranes. His group has also designed the first examples of
177:, where he is the Toby Herfindal Presidential Professor of Entrepreneurship and Innovation. He is also a member of the Cardiovascular Research Institute and an adjunct member of the Institute for Neurodegenerative Diseases at UCSF.
106:, where he is the Toby Herfindal Presidential Professor of Entrepreneurship and Innovation in the Department of Pharmaceutical Chemistry. As an early pioneer of protein design, he coined the term
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Zhu, Yongjin; Alonso, Darwin O. V.; Maki, Kosuke; Huang, Cheng-Yen; Lahr, Steven J.; Daggett, Valerie; Roder, Heinrich; DeGrado, William F.; Gai, Feng (December 11, 2003).
1515:
170:, where he was a professor in the biochemistry and biophysics department as well as an adjunct professor in the department of chemistry. Since 2011 he has been at the
166:
as a research chemist, eventually becoming a senior director for small molecule therapeutics in DuPont Merck's medicinal chemistry department. In 1995 he moved to the
131:
while working as a commercial artist at Solo. In appreciation, Solo Cup offered DeGrado, a scholarship for the final two years of college, which DeGrado completed at
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1983:
1977:
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Bach, Alvin C.; Espina, J. Robert; Jackson, Sharon A.; Stouten, Pieter F. W.; Duke, Jodie L.; Mousa, Shaker A.; DeGrado, William F. (January 1, 1996).
2025:
2013:
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Bryson, James W.; Betz, Stephen F.; Lu, Helen S.; Suich, Daniel J.; Zhou, Hongxing X.; O'Neil, Karyn T.; DeGrado, William F. (November 10, 1995).
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Qin, Haiying; Edwards, Justin P.; Zaritskaya, Liubov; Gupta, Ankit; Mu, C. Jenny; Fry, Terry J.; Hilbert, David M.; LaFleur, David W. (2019).
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1007:"Chimeric Antigen Receptors Incorporating D Domains Targeting CD123 Direct Potent Mono- and Bi-specific Antitumor Activity of T Cells"
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Reed, Nilgun I.; Jo, Hyunil; Chen, Chun; Tsujino, Kazuyuki; Arnold, Thomas D.; DeGrado, William F.; Sheppard, Dean (May 20, 2015).
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protein design. He is also active in discovery of small molecule drugs for a variety of human diseases. He is a member of the
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1186:"De Novo Design of Antimicrobial Polymers, Foldamers, and Small Molecules: From Discovery to Practical Applications"
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Mousa, Shaker A.; DeGrado, William F.; Mu, Dun-Xu; Kapil, Ram P.; Lucchesi, Benedict R.; Reilly, Thomas M. (1996).
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Walsh, Scott T. R.; Cheng, Hong; Bryson, James W.; Roder, Heinrich; DeGrado, William F. (May 11, 1999).
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Chung, Hoi Sung; Piana-Agostinetti, Stefano; Shaw, David E.; Eaton, William A. (September 25, 2015).
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1282:"Oral Antiplatelet, Antithrombotic Efficacy of DMP 728, a Novel Platelet GPIIb/IIIa Antagonist"
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Tew, Gregory N.; Scott, Richard W.; Klein, Michael L.; DeGrado, William F. (January 19, 2010).
1055:"Master Protocol for the Phase 1 Study of Cell Therapies in Multiple Myeloma - Full Text View"
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protein, alpha3D, was notable at the time, because it was the premier example of a
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517:"Solution structure and dynamics of a de novo designed three-helix bundle protein"
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2020 The
Franklin Institute & City Council of Philadelphia John C. Scott Award
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2008 The
American Chemical Society Ralph F. Hirschmann Award in Peptide Chemistry
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Cheng, Richard P.; Gellman, Samuel H.; DeGrado, William F. (October 1, 2001).
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924:"De Novo Protein Design as a Methodology for Synthetic Bioinorganic Chemistry"
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DeGrado, William F.; Wasserman, Zelda R.; Lear, James D. (February 3, 1989).
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857:"Ultrafast folding of α3D: A de novo designed three-helix bundle protein"
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1329:"The α v β 1 integrin plays a critical in vivo role in tissue fibrosis"
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344:"Characterization of a Helical Protein Designed from First Principles"
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1243:"Type II' to Type I β-Turn Swap Changes Specificity for Integrins"
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1988 Du
Vigneaud Award for Young Investigators in Peptide Research
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Starting in the 1980's DeGrado's group developed the approach of
262:
1995 Fellow, American
Association for the Advancement of Science
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163:
316:
922:
Mocny, Catherine S.; Pecoraro, Vincent L. (August 18, 2015).
698:"De Novo Protein Design: Fully Automated Sequence Selection"
229:
122:. He also is a scientific cofounder of Pliant therapeutics.
1503:
1436:"Recipients | ACS Division of Biological Chemistry Website"
980:"Arcellx Cell Therapies for Cancer and Autoimmune Diseases"
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2058:
Members of the United States
National Academy of Sciences
1004:
1384:
1240:
792:"Structural origin of slow diffusion in protein folding"
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Dahiyat, Bassil I.; Mayo, Stephen L. (October 3, 1997).
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DeGrado contributed significantly to the development of
66:
De novo protein design and small molecule drug discovery
1047:
280:
2015 The Stein & Moore Award of the
Protein Society
154:
After receiving his PhD in organic chemistry from the
584:"De novo design of the hydrophobic cores of proteins"
514:
342:
Regan, Lynne; DeGrado, William F. (August 19, 1988).
142:(1978) and a doctorate in organic chemistry from the
1183:
396:
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Search for publications from W.F. DeGrado on Pubmed
1411:"The Protein Society : Protein Society Awards"
1403:
1279:
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283:
2016 Weizmann
Institute Max Perutz Memorial Lecture
1080:Korendovych, Ivan V.; DeGrado, William F. (2020).
1079:
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271:2003 The American Peptide Society Merrifield Award
268:1999 Member, National Academy of Sciences (U.S.A.)
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149:
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277:2009 The American Peptide Society Makineni Award
226:which is currently in phase II clinical trials.
861:Proceedings of the National Academy of Sciences
521:Proceedings of the National Academy of Sciences
743:Ponder, Jay W.; Richards, Frederic M. (1987).
742:
582:Desjarlais, John R.; Handel, Tracy M. (1995).
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639:Dahiyat, Bassil I.; Mayo, Stephen L. (1996).
250:1989 Protein Society Young Investigator Award
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138:DeGrado received his B.A. in chemistry from
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321:UCSF Department of Pharmaceutical Chemistry
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1082:"De novo protein design, a retrospective"
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230:Contributions to Pharmaceutical Chemistry
199:proteins for treatment of human disease.
1247:Journal of the American Chemical Society
1139:"β-Peptides: From Structure to Function"
317:"Department of Pharmaceutical Chemistry"
1505:Eli Lilly Award in Biological Chemistry
454:"Protein Design: A Hierarchic Approach"
399:"Protein Design, a Minimalist Approach"
255:Eli Lilly Award in Biological Chemistry
172:University of California, San Francisco
116:American Academy of Arts & Sciences
104:University of California, San Francisco
89:University of California, San Francisco
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81:Chemistry, Biochemistry and Biophysics
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292:2018 The American Chemical Society
286:2018 The American Chemical Society
13:
2053:University of Pennsylvania faculty
102:(born 1955) is a professor at the
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1464:Website of the DeGrado laboratory
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745:"Tertiary templates for proteins"
112:U.S. National Academy of Sciences
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1086:Quarterly Reviews of Biophysics
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259:1993 DuPont Merck Summit Award
158:(1981) under the direction of
150:Industrial and academic career
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1190:Accounts of Chemical Research
928:Accounts of Chemical Research
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294:Murray Goodman Memorial Prize
120:National Academy of Inventors
1345:10.1126/scitranslmed.aaa5094
940:10.1021/acs.accounts.5b00175
761:10.1016/0022-2836(87)90358-5
749:Journal of Molecular Biology
478:10.1126/science.270.5238.935
7:
1023:10.1016/j.ymthe.2019.04.010
714:10.1126/science.278.5335.82
641:"Protein design automation"
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168:University of Pennsylvania
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1098:10.1017/S0033583519000131
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222:ion and proton channels.
93:
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162:, DeGrado began work at
126:Early life and Education
1298:10.1161/01.cir.93.3.537
882:10.1073/pnas.2136623100
816:10.1126/science.aab1369
542:10.1073/pnas.96.10.5486
423:10.1126/science.2464850
368:10.1126/science.3043666
657:10.1002/pro.5560050511
600:10.1002/pro.5560041006
202:With Angela Lombardi (
100:William (Bill) DeGrado
1708:Charles C. Richardson
156:University of Chicago
144:University of Chicago
58:University of Chicago
2063:American biochemists
1972:Christopher J. Chang
1948:Paul J. Hergenrother
1924:Benjamin Cravatt III
1822:Jacqueline K. Barton
1774:Christopher T. Walsh
204:University of Naples
1930:Dewey G. McCafferty
1858:Stuart L. Schreiber
1792:Harold M. Weintraub
1696:Phillips W. Robbins
1440:www.divbiolchem.org
1415:The Protein Society
873:2003PNAS..10015486Z
867:(26): 15486–15491.
808:2015Sci...349.1504C
802:(6255): 1504–1510.
533:1999PNAS...96.5486W
470:1995Sci...270..935B
415:1989Sci...243..622D
360:1988Sci...241..976R
1954:Scott K. Silverman
1936:Linda Hsieh-Wilson
1918:Andreas Matouschek
1876:Gregory L. Verdine
1840:George L. McLendon
1642:Harold A. Scheraga
1552:Earl A. Evans, Jr.
1061:. November 7, 2019
1059:ClinicalTrials.gov
986:. February 6, 2023
323:. January 10, 2017
288:Cope Scholar Award
175:School of Pharmacy
56:Kalamazoo College
22:William F. DeGrado
2035:
2034:
2008:Bradley Pentelute
1978:Matthew D. Disney
1786:Roger D. Kornberg
1768:Charles R. Cantor
1744:James E. Dahlberg
1714:Mario R. Capecchi
1690:Gerald M. Edelman
1678:William P. Jencks
1636:Robert A. Alberty
1630:William F. Neuman
1558:Herbert E. Carter
1391:. January 5, 2023
1259:10.1021/ja953163+
1202:10.1021/ar900036b
1155:10.1021/cr000045i
1149:(10): 3219–3232.
1011:Molecular Therapy
594:(10): 2006–2018.
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265:1998 Fellow, AAAS
140:Kalamazoo College
133:Kalamazoo College
97:
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72:Scientific career
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1882:Alanna Schepartz
1846:Peter G. Schultz
1816:James E. Rothman
1804:David V. Goeddel
1780:Phillip A. Sharp
1762:Robert G. Roeder
1732:Bruce M. Alberts
1702:Gordon G. Hammes
1618:Nathan O. Kaplan
1606:John M. Buchanan
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2026:Jordan L. Meier
2014:Neal K. Devaraj
1996:Elizabeth Nolan
1912:Kevan M. Shokat
1906:Jennifer Doudna
1852:William DeGrado
1810:Gerald M. Rubin
1726:David F. Wilson
1666:Frederick Crane
1612:David M. Bonner
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1864:Peter S. Kim
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1798:Richard Axel
1750:Mark Ptashne
1660:James Watson
1624:Harvey Itano
1540:Eric G. Ball
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2068:1955 births
2002:Howard Hang
1738:C. Fred Fox
1534:George Wald
1420:February 8,
1395:February 8,
1286:Circulation
1065:February 8,
990:February 8,
327:February 8,
118:(1997) and
45:Nationality
2042:Categories
1990:Minkui Luo
1684:Bruce Ames
303:References
236:Brilacidin
208:Les Dutton
2020:Yimon Aye
1654:Paul Berg
1445:March 22,
1353:1946-6234
1306:0009-7322
1267:0002-7863
1210:0001-4842
1163:0009-2665
1106:0033-5835
948:0001-4842
891:0027-8424
824:0036-8075
769:0022-2836
722:0036-8075
665:0961-8368
608:0961-8368
551:0027-8424
486:0036-8075
431:0036-8075
376:0036-8075
1385:"Pliant"
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1228:19813703
1171:11710070
1124:32041676
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569:10318910
502:31116489
181:Research
146:(1981).
114:(1999),
48:American
1984:Yi Tang
1362:4461057
1314:8565173
1219:2808429
1115:7243446
1032:6612629
984:Arcellx
957:5257248
869:Bibcode
833:6260792
804:Bibcode
796:Science
777:2441069
730:9311930
702:Science
683:8732761
674:2143401
626:8535237
617:2142989
529:Bibcode
494:7481798
466:Bibcode
458:Science
439:2464850
411:Bibcode
403:Science
384:3043666
356:Bibcode
348:Science
220:de novo
197:de novo
192:de novo
187:de novo
108:de novo
2028:(2021)
2022:(2020)
2016:(2019)
2010:(2018)
2004:(2017)
1998:(2016)
1992:(2015)
1986:(2014)
1980:(2013)
1974:(2012)
1968:(2011)
1962:(2010)
1956:(2009)
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