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Macromolecular Therapeutics

Emerging Strategies for Drug Discovery in the Postgenome Era

Department of Pharmacology School of Medicine and Program in Macromolecular Therapeutics University of North Carolina Chapel Hill NC 27599

Correspondence: Address correspondence to RLJ. E-mail arjay{at}med.unc.edu; fax (919) 966-5640.

The postgenome era offers a plethora of potential therapeutic targets. Many of these targets will be addressable using small organic molecules as drug candidates. However, certain aspects of cell function, particularly those that rely on protein–protein or protein–nucleic acid interactions, will be difficult to influence using small molecules. Thus, the possibility of using highly specific macromolecules as potential therapeutic agents is an intriguing concept. Recent developments in several areas of research have brought this possibility closer to fruition. Peptide and nucleic acid combinatorial libraries allow the generation of novel molecules having exquisite selectivity. Structural information and molecular modeling also contribute to the design of new macromolecules with therapeutic potential. Perhaps most importantly, approaches for delivering macromolecules into the cell interior have been developed and applied with considerable success. Thus, the therapeutic use of macromolecules, including oligonucleotides, peptides, and proteins, may be an idea whose time has come.

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