Nonpeptidic compounds

Recently, nonpeptide compounds have been developed for many peptide receptor systems. These compounds, which usually are discovered through screening of chemical files, generally do not resemble the corresponding peptide ligands chemically. Nevertheless, they act as specific and... 

In the first phase of their research, Squibb tested a short-chain peptide isolated from the venom of the viper Bothrops jararaca, with which Vane was working in the laboratory, in human volunteers and showed that it did, indeed, inhibit the conversion of angiotensin I to angiotensin II after intravenous injection. The peptide was also shown to reduce blood pressure in patients when injected. Since the vast majority of peptides cannot be absorbed from the GI tract, Squibb scientists set out to prepare a nonpeptide compound that could be used orally and manufactured at acceptable cost. The design of a true peptidomimetic that became orally active had not been accomplished at that time. Squibb then carried out... 

The low oral bioavailability, the susceptibility to proteolytic breakdown, and the inability to pass through the blood-brain barrier make peptides of less general utility as pharmaceutical leads as compared to nonpeptidic compounds. Substituted heterocyclic compounds offer a high degree of structural diversity and have proven to be broadly useful as therapeutic agents. In the last decade, the design and development of... 

Labrosse, B. Xreboute, C. Alizon, M. Sensitivity to a nonpeptidic compound (RPR103611) blocking human immunodeficiency virus type 1 Env-mediated fusion depends on sequence and accessibility of the gp41 loop region. J. Virol, 2000, 74 2142-2150. 

Irie, M., Terada, T., Sawada, K., Saito, H. and Inui, K. (2001) Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells. The Journal of Pharmacology and Experimental Therapeutics, 298, 711—717. 

Profile TPIMS is a nonprofit biomedical research institute focused on the development of combinatorial chemistry techniques that can be applied to all compound types. It was founded in 1988 to continue earlier research begun at The Scripps Research Institute in La Jolla, California, and in 1989 it began its research activities. Less than one year after beginning its operations, TPIMS scientists had developed a method for synthesizing and screening combinatorial libraries of tens of millions of peptides and other nonpeptide compounds. As a result of this early research, TPIMS became an internationally recognized research center in the field of molecular diversity and combinatorial chemistry. Research is funded by the National Institutes of Health, the National Science Foundation, the U.S. Army, and by a variety of pharmaceutical companies. 

The field of proteomics is becoming increasingly important as genome sequences are being completed and annotated (33-42,378-383). The discovery of hundreds of thousands of new proteins and peptides will provide the opportunity to map out complex cellular interactions at an unprecedented level of detail. Furthermore, with the advent of the field of proteinomimetics, which utilizes peptide-based molecules to mimic native protein function, many new and novel peptide and nonpeptide compounds will find niches as pharmaceutical drugs (383-386). 

The only truly nonpeptidic compound among cliiucally approved HIV Pis is tipranavir (TPV, PNU-140690, approved under the name Aptivus), which was designed at Pharmacia Upjohn and... 

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