Richard A. Houghten
Encyclopedia
Richard A. Houghten is a heterocyclic organic chemist and founder of the journal Peptide Research, which was later merged with the International Journal of Peptide and Protein Research, to become the Journal of Peptide Research. His work mainly concerns peptide
activity and pharmacology
. He is the founder and president of the Torrey Pines Institute for Molecular Studies
(TPIMS), a biomedical research institute. Houghten pioneered the "tea-bag" approach of producing peptides for pharmacological work.
He is author of over five hundred scientific papers, 38 of which have been cited at least one hundred times. His h-index
is over 60.
from the University of California, Berkeley
in 1975. He had previously received a BS in chemistry from California State University, Fresno
and an M.S. in Chemistry from Berkeley. He held a postdoctoral fellowship at the University of California, San Francisco
, then an assistant professorship at Mount Sinai School of Medicine
, City University of New York
, and then joined the Scripps Research Institute, La Jolla, working with Richard Lerner
. Houghten branched out to the business world in the 1980s, forming Multiple Peptide Systems in 1986, the Torrey Pines Institute for Molecular Studies (TPIMS) in 1988 and Houghten Pharmaceuticals, Inc. in 1990.
is the generation of large numbers of molecules (usually peptides, enzyme
s or other polypeptides in biology) with non-natural metabolic pathway
s. The resulting set of molecules is referred to as a library. Because traditional methods of chemical discovery and selection relied on "natural" pathways (those formed by sources found in the wild and brought into the library), creation of the requisite number of peptides for new drug discovery
was impractical. New drugs needed to be built from specific combinations of protein
s among the trillions of possible combinations. Synthetic avenues for peptide generation became an important venue for drug creation in the 1980s.
In 1985, Houghten's most cited paper (cited 650 times, according to Scopus
) published his method for the synthesis of massive numbers of peptides—enough for practical use in pharmacological work—in the Proceedings of the National Academy of Sciences
. This method was referred to as the "tea-bag" method because deprotected peptides are enclosed in mesh bags and dipped quickly into liquid solutions containing activated amino acids (or other organic compounds). The peptide is thus elongated one amino acid at each step, and by careful movement of each teabag, a series of related peptides can be made. By another variation, "split and mix", tens of millions of very diverse peptides can be made, and then assayed by some technique. Very precise deconvolution of the results, or alternatively, marking the peptide beads, can correlate sequence and activity. This allowed "[the capture of] information in a day that you couldn't get in a hundred years before" according to Houghten.
The problem of generating and sequencing large libraries of peptides suitable for pharmaceutical work remained. Selection and identification of specific desired molecular traits (e.g. antigen response, antimicrobial response) required a selection algorithm and process. In 1991, he and his colleagues published one of the major papers in combinatorial biology—the paper described a method to generate peptides capturable to contemporary protein microarray
s through the creation of synthetic peptide combinatorial libraries (SPCL).
Houghten continued his work in combinatorial biology with an article in Methods, the journals section of Methods in Enzymology
. which is the standard multi-volume references set for biochemical methodology in research.
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...
activity and pharmacology
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
. He is the founder and president of the Torrey Pines Institute for Molecular Studies
Torrey Pines Institute for Molecular Studies
The Torrey Pines Institute for Molecular Studies, also commonly referred to as TPIMS, is a non-profit biomedical research institute "dedicated to the discovery of causes, treatments and cures for a wide variety of diseases and afflictions including heart disease, cancer, AIDS, diabetes, multiple...
(TPIMS), a biomedical research institute. Houghten pioneered the "tea-bag" approach of producing peptides for pharmacological work.
He is author of over five hundred scientific papers, 38 of which have been cited at least one hundred times. His h-index
H-index
The h-index is an index that attempts to measure both the productivity and impact of the published work of a scientist or scholar. The index is based on the set of the scientist's most cited papers and the number of citations that they have received in other publications...
is over 60.
Biography
Houghten received his PhD in organic chemistryOrganic 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 University of California, Berkeley
University of California, Berkeley
The University of California, Berkeley , is a teaching and research university established in 1868 and located in Berkeley, California, USA...
in 1975. He had previously received a BS in chemistry from California State University, Fresno
California State University, Fresno
California State University, Fresno, often referred to as Fresno State University and synonymously known in athletics as Fresno State , is one of the leading campuses of the California State University system, located at the northeast edge of Fresno, California, USA.The campus sits at the foot of...
and an M.S. in Chemistry from Berkeley. He held a postdoctoral fellowship at the University of California, San Francisco
University of California, San Francisco
The University of California, San Francisco is one of the world's leading centers of health sciences research, patient care, and education. UCSF's medical, pharmacy, dentistry, nursing, and graduate schools are among the top health science professional schools in the world...
, then an assistant professorship at Mount Sinai School of Medicine
Mount Sinai School of Medicine
Mount Sinai School of Medicine is an American medical school in the borough of Manhattan in New York City, currently ranked among the top 20 medical schools in the United States. It was chartered by Mount Sinai Hospital in 1963....
, City University of New York
City University of New York
The City University of New York is the public university system of New York City, with its administrative offices in Yorkville in Manhattan. It is the largest urban university in the United States, consisting of 23 institutions: 11 senior colleges, six community colleges, the William E...
, and then joined the Scripps Research Institute, La Jolla, working with Richard Lerner
Richard Lerner
Richard A. Lerner is an American research chemist. Best known for his work on catalytic antibodies, Lerner is currently President of The Scripps Research Institute , and a member of its Skaggs Institute for Chemical Biology, in La Jolla, California.-Biography:Lerner grew up in Chicago and...
. Houghten branched out to the business world in the 1980s, forming Multiple Peptide Systems in 1986, the Torrey Pines Institute for Molecular Studies (TPIMS) in 1988 and Houghten Pharmaceuticals, Inc. in 1990.
Awards
- Vincent du Vigneaud Award for Excellence in Peptide Science (2000) http://www.americanpeptidesociety.org/pages/awards.asp
- American Chemical Society's Ralph F. Hirschmann Award in Peptide Chemistry (2004) https://portal.acs.org/preview/appmanager/corg/memberapp?_nfpb=true&_pageLabel=PP_ARTICLEMAIN&node_id=1319&content_id=CTP_004547&use_sec=true&sec_url_var=region1
- Bruce Merrifield Award (2005) http://www.americanpeptidesociety.org/pages/awards.asp
- Fellow of the American Association of Pharmaceutical Scientists (2006) http://www.aapspharmaceutica.com/about/press/NewsEntry/PressReleaseView.asp?ID=141
- Dan K. Richardson Entrepreneurship Program's 2011 Entrepreneur of the Year http://www.irscfoundation.org/p/42/community-programs
Work in combinatorial biology
Combinatorial biologyCombinatorial biology
In biotechnology, combinatorial biology is the creation of a large number of compounds through technologies such as phage display. Similar to combinatorial chemistry, compounds are produced by biosynthesis rather than organic chemistry. This process was developed independently by Richard A....
is the generation of large numbers of molecules (usually peptides, enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s or other polypeptides in biology) with non-natural metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
s. The resulting set of molecules is referred to as a library. Because traditional methods of chemical discovery and selection relied on "natural" pathways (those formed by sources found in the wild and brought into the library), creation of the requisite number of peptides for new drug discovery
Drug development
Drug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...
was impractical. New drugs needed to be built from specific combinations of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s among the trillions of possible combinations. Synthetic avenues for peptide generation became an important venue for drug creation in the 1980s.
In 1985, Houghten's most cited paper (cited 650 times, according to Scopus
Scopus
Scopus, officially named SciVerse Scopus, is a bibliographic database containing abstracts and citations for academic journal articles. It covers nearly 18,000 titles from over 5,000 international publishers, including coverage of 16,500 peer-reviewed journals in the scientific, technical, medical,...
) published his method for the synthesis of massive numbers of peptides—enough for practical use in pharmacological work—in the Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences...
. This method was referred to as the "tea-bag" method because deprotected peptides are enclosed in mesh bags and dipped quickly into liquid solutions containing activated amino acids (or other organic compounds). The peptide is thus elongated one amino acid at each step, and by careful movement of each teabag, a series of related peptides can be made. By another variation, "split and mix", tens of millions of very diverse peptides can be made, and then assayed by some technique. Very precise deconvolution of the results, or alternatively, marking the peptide beads, can correlate sequence and activity. This allowed "[the capture of] information in a day that you couldn't get in a hundred years before" according to Houghten.
The problem of generating and sequencing large libraries of peptides suitable for pharmaceutical work remained. Selection and identification of specific desired molecular traits (e.g. antigen response, antimicrobial response) required a selection algorithm and process. In 1991, he and his colleagues published one of the major papers in combinatorial biology—the paper described a method to generate peptides capturable to contemporary protein microarray
Protein microarray
A protein microarray, sometimes referred to as a protein binding microarray,provides a multiplex approach to identify protein–protein interactions, to identify the substrates of protein kinases, to identify transcription factor protein-activation, or to identify the targets of biologically active...
s through the creation of synthetic peptide combinatorial libraries (SPCL).
Houghten continued his work in combinatorial biology with an article in Methods, the journals section of Methods in Enzymology
Methods in Enzymology
Methods in Enzymology is a series of scientific publications focused primarily on research methods in biochemistry by Academic Press, created by Sidney P. Colowick and Nathan O. Kaplan, now part of Elsevier. Historically, each volume has centered on a specific topic of biochemistry, such as DNA...
. which is the standard multi-volume references set for biochemical methodology in research.