Julius Rebek
Encyclopedia
Hungary
Hungary , officially the Republic of Hungary , is a landlocked country in Central Europe. It is situated in the Carpathian Basin and is bordered by Slovakia to the north, Ukraine and Romania to the east, Serbia and Croatia to the south, Slovenia to the southwest and Austria to the west. The...
-born American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
and expert on molecular self-assembly
Molecular self-assembly
Molecular self-assembly is the process by which molecules adopt a defined arrangement without guidance or management from an outside source. There are two types of self-assembly, intramolecular self-assembly and intermolecular self-assembly...
.
Rebek was born in Beregszasz (Berehove), Hungary
Hungary
Hungary , officially the Republic of Hungary , is a landlocked country in Central Europe. It is situated in the Carpathian Basin and is bordered by Slovakia to the north, Ukraine and Romania to the east, Serbia and Croatia to the south, Slovenia to the southwest and Austria to the west. The...
in 1944 and lived in Austria
Austria
Austria , officially the Republic of Austria , is a landlocked country of roughly 8.4 million people in Central Europe. It is bordered by the Czech Republic and Germany to the north, Slovakia and Hungary to the east, Slovenia and Italy to the south, and Switzerland and Liechtenstein to the...
from 1945 to 1949. In 1949 he and his family immigrated to the United States
Immigration to the United States
Immigration to the United States has been a major source of population growth and cultural change throughout much of the history of the United States. The economic, social, and political aspects of immigration have caused controversy regarding ethnicity, economic benefits, jobs for non-immigrants,...
and settled in Kansas
Kansas
Kansas is a US state located in the Midwestern United States. It is named after the Kansas River which flows through it, which in turn was named after the Kansa Native American tribe, which inhabited the area. The tribe's name is often said to mean "people of the wind" or "people of the south...
. Rebek graduated from the University of Kansas
University of Kansas
The University of Kansas is a public research university and the largest university in the state of Kansas. KU campuses are located in Lawrence, Wichita, Overland Park, and Kansas City, Kansas with the main campus being located in Lawrence on Mount Oread, the highest point in Lawrence. The...
with a Bachelor of Arts
Bachelor of Arts
A Bachelor of Arts , from the Latin artium baccalaureus, is a bachelor's degree awarded for an undergraduate course or program in either the liberal arts, the sciences, or both...
degree
Academic degree
An academic degree is a position and title within a college or university that is usually awarded in recognition of the recipient having either satisfactorily completed a prescribed course of study or having conducted a scholarly endeavour deemed worthy of his or her admission to the degree...
in chemistry. Rebek received his Master of Arts
Master of Arts (postgraduate)
A Master of Arts from the Latin Magister Artium, is a type of Master's degree awarded by universities in many countries. The M.A. is usually contrasted with the M.S. or M.Sc. degrees...
degree and his Ph.D.
Doctor of Philosophy
Doctor of Philosophy, abbreviated as Ph.D., PhD, D.Phil., or DPhil , in English-speaking countries, is a postgraduate academic degree awarded by universities...
in organic chemistry
Organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
from the Massachusetts Institute of Technology
Massachusetts Institute of Technology
The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...
in 1970. There he studied peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s under D.S. Kemp.
Rebek was an assistant professor
Professor
A professor is a scholarly teacher; the precise meaning of the term varies by country. Literally, professor derives from Latin as a "person who professes" being usually an expert in arts or sciences; a teacher of high rank...
at the University of California at Los Angeles from 1970 to 1976. There he developed the three-phase test for reactive intermediate
Reactive intermediate
In chemistry a reactive intermediate is a short-lived, high energy, highly reactive molecule. When generated in a chemical reaction it will quickly convert into a more stable molecule. Only in exceptional cases can these compounds be isolated and stored, e.g. low temperatures, matrix isolation...
s. In 1976, he moved to the University of Pittsburgh
University of Pittsburgh
The University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...
, where he developed cleft
Cleft
Cleft lip and cleft palate , which can also occur together as cleft lip and palate, are variations of a type of clefting congenital deformity caused by abnormal facial development during gestation. A cleft is a fissure or opening—a gap. It is the non-fusion of the body's natural structures that...
-like structures for studies in molecular recognition
Molecular recognition
The term molecular recognition refers to the specific interaction between two or more molecules through noncovalent bonding such as hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, π-π interactions, electrostatic and/or electromagnetic effects...
. In 1989 he returned to MIT, where he became the Camille Dreyfus Professor of Chemistry and devised synthetic, self-replicating
Self-replication
Self-replication is any behavior of a dynamical system that yields construction of an identical copy of that dynamical system. Biological cells, given suitable environments, reproduce by cell division. During cell division, DNA is replicated and can be transmitted to offspring during reproduction...
molecules. In July 1996, he moved his research group to the Scripps Research Institute to become the director of the Skaggs Institute for Chemical Biology, where he continues to work in molecular recognition and self-assembling systems.
Rebek is a member of the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
.
Three-phase test
Rebek’s independent research began in 1970s, with a method to detect reactive intermediates. This was invented through application of polymerPolymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
-bound reagents. A precursor for the reactive intermediate was covalently attached to one solid phase while a trap was attached to a second such support. When transfer takes place between the solid phases, it requires the existence of a reactive intermediate, free in solution as shown below. Among the reactive species detected by this “Three Phase Test” were cyclobutadiene, singlet oxygen, monomeric metaphosphate, and acyl imidazoles.
Molecular machine
A model of the Pauling principleLinus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...
- catalysis by maximum binding to the transition state – was devised in 1978. A physical processes, the racemization of the bipyridyl shown below was chosen. The transition structure features coplanar aryl rings and a binding force — the chelation of a metal by bipyridyl —shows maximum metal/ligand attraction at the coplanar geometry.
The biaryl bond acts like a fulcrum and binding induces a mechanical stress elsewhere in a molecule. This was one of the first molecular machines, a rotor.
Synthetic model of allosteric effects
Other bipyridyls and biphenyls were designed in the 1980s as synthetic models of allosteric effects shown below. One involved two identical and mechanically coupled binding sites and it showed positive cooperativity in binding of covalent mercury compounds.Rotors are still the most frequent chemical models for allosteric effects, and are present in many of the molecular machines pursued in other laboratories today.
Molecular recognition
Efforts in molecular recognition in the 1980s, led to cleft-like shapesfor recognition of ions and especially nonionic targets. Using derivatives of Kemp’s triacid, Rebek arranged functional groups that “converged” to create a recognition site. Shown above is a bisimide that chelates adenine in water.
Versions with carboxyl groups became widely used elsewhere as models for metalloenzymes (the XDK structures)
and in Rebek’s laboratory to probe stereoelectronic effects.
Self-replication
In 1990, these studies culminated in a synthetic, self-complementary that acted as a template for its own formation. It showed autocatalysis based on molecular recognition and was the first synthetic system to show a primitive sign of life: self-replication.The template grasps the reactants by hydrogen bonding at both ends as indicated below. The self-complementary “recipe” has been incorporated universally in self-replicating systems synthesized in other research groups.
Philip Ball
Philip Ball
Philip Ball is an English science writer. He holds a degree in chemistry from Oxford and a doctorate in physics from Bristol University. He was an editor for the journal Nature for over 10 years. He now writes a regular column in Chemistry World...
in his book, Designing the Molecular World, argues that Rebek's self replicating molecules share some criteria with both nucleic acids and proteins and, moreover, “their replications operates according to novel kind of molecular interaction rather than mimicking the complementarity base pairing of nucleic acids. One could view this as an indication that perhaps DNA is not the sine qua none of life, so that one might conceive of organisms that "live" according to completely different molecular principles.” He suggests that Rebek has been able to pursue the idea of “molecular “evolution” by making artificial replicators that can be mutated. … The considerable excitement that has greeted Julius Rebek’s work is inspired in part by the possibilities that it raises for exploring the kind of chemical processes that led to the appearance of life on our planet.”
British ethologist Richard Dawkins
Richard Dawkins
Clinton Richard Dawkins, FRS, FRSL , known as Richard Dawkins, is a British ethologist, evolutionary biologist and author...
in his book, River out of Eden
River out of Eden
River Out of Eden: A Darwinian View of Life is a 1995 popular science book by Richard Dawkins. The book is about Darwinian evolution and includes summaries of the topics covered in his earlier books, The Selfish Gene, The Extended Phenotype and The Blind Watchmaker. It is part of the Science...
, suggests that Rebek's replicating molecules “raise the possibility of other worlds having a parallel evolution [to Earth's] but with a fundamentally different chemical basis."
Self assembly
Through collaboration with Javier de Mendoza in 1993, Rebek managed to create a self-assembling capsule. These form reversibly by completely surrounding small molecule targetsand have become a versatile tool of modern physical organic chemistry
Physical organic chemistry
Physical organic chemistry is the study of the interrelationships between structure and reactivity in organic molecules. It can be seen as the study of organic chemistry using tools of physical chemistry such as chemical equilibrium, chemical kinetics, thermochemistry, and quantum chemistry...
. They exist in solution at equilibrium and under ambient conditions. They act as nanometric reaction chambers, as means to stabilize reagents, as sources of “complexes within complexes” and as spaces where new forms of stereochemistry have been created. They also inspired encapsulation in other research groups that use metal-ligand interactions for self-assembly. A cylindrical capsule of nanometric dimensions is shown above; it selects congruent guests singly or pairwise when the space inside is appropriately filled.
Richard Dawkins writes about autocatalysis as a potential explanation for abiogenesis
Abiogenesis
Abiogenesis or biopoesis is the study of how biological life arises from inorganic matter through natural processes, and the method by which life on Earth arose...
in his 2004 book The Ancestor's Tale. He cites experiments performed by Julius Rebek and his colleagues at the Scripps Research Institute in California in which they combined amino adenosine and pentafluorophenyl ester with the autocatalyst amino adenosine triacid ester (AATE). One system from the experiment contained variants of AATE which catalysed the synthesis of themselves. This experiment demonstrated the possibility that autocatalysts could exhibit competition within a population of entities with heredity, which could be interpreted as a rudimentary form of natural selection.
Protein Surface Mimetics
In recent years Rebek has pursued synthetic protein surface mimetics.Through a collaboration with Tamas Bartfai, these show promising biological activity in animal models of diseases.
Positions held
- 1970-1976: Assistant Professor, University of California Los Angeles, Los Angeles, CA
- 1976-1979: Associate Professor, University of Pittsburgh, Pittsburgh, PA
- 1980-1989: Professor, University of Pittsburgh, Pittsburgh, PA
- 1989-1991: Professor, Massachusetts Institute of Technology, Cambridge, MA
- 1991-1996: Camille Dreyfus Prof. of Chemistry Massachusetts Institute of Technology, Cambridge, MA
- 1996–present: Director, Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA
Honors
- 1967-1970: National Science FoundationNational Science FoundationThe National Science Foundation is a United States government agency that supports fundamental research and education in all the non-medical fields of science and engineering. Its medical counterpart is the National Institutes of Health...
pre-doctoral fellow - 1976-1974: Eli Lilly Award
- 1976-1978: A.P. Sloan FellowAlfred P. Sloan FoundationThe Alfred P. Sloan Foundation is a philanthropic non-profit organization in the United States. It was established in 1934 by Alfred P. Sloan, Jr., then-President and Chief Executive Officer of General Motors.-Overview:...
- 1981: Alexander von Humboldt Fellow
- 1986: Guggenheim Fellow
- 1990: Myron L. BenderMyron L. BenderMyron Lee Bender was born in St. Louis, Missouri. He obtained his B.S. and his Ph.D. from Purdue University. The latter was under the direction of Henry B. Hass. After postdoctoral research under Paul D. Barlett , and Frank H. Westheimer , he spent one year as a faculty member at the...
and Muriel S. Bender Distinguished Summer Lecturer in Organic Chemistry, Northwestern UniversityNorthwestern UniversityNorthwestern University is a private research university in Evanston and Chicago, Illinois, USA. Northwestern has eleven undergraduate, graduate, and professional schools offering 124 undergraduate degrees and 145 graduate and professional degrees.... - 1991: A.C. Cope Scholar Award
- 1993: American Academy of Arts and SciencesAmerican Academy of Arts and SciencesThe American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
- 1994: National Academy of Science
- 1996: MERIT Award (National Institutes of HealthNational Institutes of HealthThe National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
) - 1997: James Flack Norris Award in Physical Organic Chemistry (American Chemical SocietyAmerican Chemical SocietyThe American Chemical Society is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 161,000 members at all degree-levels and in all fields of chemistry, chemical...
) - 2001: Hungarian Academy of SciencesHungarian Academy of SciencesThe Hungarian Academy of Sciences is the most important and prestigious learned society of Hungary. Its seat is at the bank of the Danube in Budapest.-History:...
- 2002: Chemical Pioneer Award (American Institute of ChemistsAmerican Institute of ChemistsThe American Institute of Chemists is an organization founded in 1923 whose goal is to advance the chemical profession in the United States. The institute is known for its yearly awards recognizing contributions of individuals in this field of work. The American Institute of Chemists Gold Medal is...
) - 2004: Ronald Breslow Award for Achievement in Biomimetic Chemistry (American Chemical SocietyAmerican Chemical SocietyThe American Chemical Society is a scientific society based in the United States that supports scientific inquiry in the field of chemistry. Founded in 1876 at New York University, the ACS currently has more than 161,000 members at all degree-levels and in all fields of chemistry, chemical...
) - 2005: Medal of the Academy of Sciences; Prague, Czech Republic
- 2005: Medal of the National Academy of Sciences, Letters and Arts; Modena, Italy
- 2005: European Academy of Science (Academia EuropaeaAcademia EuropaeaAcademia Europæa is a European non-governmental scientific academy founded in 1988. Its members are scientists and scholars who collectively aim to promote learning, education and research. It publishes European Review through Cambridge Journals....
) Member