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Exploring Ramachandran and Chi Space: Conformationally Constrained Amino Acids and Peptides in the Design of Bioactive Polypeptide Ligands

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Ligand binding and concomitant changes in receptor structure provide the means to target signal transduction pathways. With appropriate refinement of the ligand's interaction with the “receptor,” one in theory could produce ligands that have greater therapeutic benefits. This review will discuss how, when these ligands are amino acids and peptides, the introduction of appropriate conformational constraints provides a powerful strategy for improved drug design. This review will discuss how various constraints on amino acids can provide a powerful tool for ligand design, determination of the three dimensional pharmacophore and new insights into receptor systems and information transduction. Through the use of constrained ligands, new information regarding their interaction with their “receptor” systems, and further refinement of the use of constraints, scientists can produce more beneficial drugs for mankind.
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Keywords: constrained amino acids; constrained peptides; drug design; ligand-receptor interactions

Document Type: Review Article

Affiliations: Department of Chemistry,University of Arizona, Tucson, AZ 85721 USA.

Publication date: 2004-11-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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