Richard A. Houghten, Ph.D.

Richard A. Houghten earned his B.S. in chemistry in 1968 from California State University, Fresno. After earning his M.S. and Ph.D. from the UC Berkeley, under Professor Henry Rapoport in 1970 and 1975, respectively, Dr. Houghten was a Postdoctoral Fellow and Research Associate with Professor Choh Hao Li at the Hormone Research Laboratory, UC San Francisco; Assistant Professor of Medicine and Biochemistry, City University of New York, Mt. Sinai School of Medicine; and Associate Member, Department of Molecular Biology, The Scripps Research Institute, La Jolla working with Richard Lerner,Ph.D. During his early years at Scripps, Dr. Houghten invented a revolutionary method for quickly synthesizing peptides hundreds of times faster than previous existing methods. Published in PNAS in 1985, it quickly became known as the "T-bag" method in which solvent permeable packets are used to sequester unique, homogeneous sequences. This achievement presaged the later global advances in combinatorial synthesis by at least 5 years. Licensed to Irori (now Discovery Technologies), the T-bag approach, renamed by Discovery Technologies MicroKans, has resulted in the synthesis of literally millions of low molecular weight compounds. Such numbers were clearly a practical impossibility with technologies preceding Dr. Houghten’s pioneering inventions.

Dr. Houghten continued to advance the development and use of synthetic libraries. His approach (Nature 1991) for generating well-defined mixtures of free peptides in amounts suitable for a wide range of pharmacological assessment remains the simplest and most widely applicable peptide library method. This is exemplified by his 1994 Science report, in which an acetylated all D-amino acid hexapeptide having high µ opioid receptor binding affinity, specificity and agonist activity, yet no structural homology to known peptide opioids, was identified from a library of 32 million hexapeptides. His "libraries from libraries" concept (PNAS 1994) and more than fifty further publications advancing this approach over the past 10 years involves the transformation of peptide libraries, while still resin bound, to generate low molecular weight heterocyclic libraries having completely different physical chemical properties from the peptide starting materials. This approach has generated leads virtually certain to be missed by standard structure-activity approaches. Further pioneering advances include the “positional scanning” approach, which enables the rapid identification of active moieties in all positions of a given chemical structure. Described in J.Biological Chemistry, an all D-amino acid tetrapeptide was identified from a positional scanning library made up of 6.25 million tetrapeptides. The active compounds identified had no sequence homology to existing compounds and remains the most kappa opiate receptor-specific compound identified to date. This compound is in late stage pre-clinical trials as an anti-inflammatory. Houghten and his colleagues have discussed these and related issues in the J. Med. Chem. (1999) Perspective.

Dr. Houghten's scholarly contributions include 550 scientific publications and 63 issued U.S. patents. He has been honored by receiving: 1996 San Diego Distinguished Scientist Award of the American Chemical Society; 1997 Advanced ChemTech Combinatorial Library Science Award; 1997 California State University, Fresno, Alumni Award of Excellence; 1998 Hewlett Packard Award for Outstanding Research in Integrated Analytical Systems; 1998 TNO Pharma Award for Outstanding Strategic Research in Combinatorial Technologies; the 2000 Vincent du Vigneaud Award in Peptide Science and the ACS 2004 Ralph Hirschmann award in Peptide Science. His acceptance of the Athena Pinnacle Award in 1999 further distinguishes Dr. Houghten and his dedication to the advancement of women scientists in the work place.

He founded the Journal Peptide Research, which was later merged with the “International Journal of Peptide and Protein Research,” to become the J. Peptide Research; is a co-founding editor of Molecular Diversity, and is on Editorial Boards of eight journals. In 2001, Richard co-hosted the 2nd International/17th APS Symposium in San Diego. Over 1,250 scientists from around the world attended, including speakers such as Craig Ventor from Celera.