Targeting growth factor and cytokine receptors with recombinant peptide libraries.
The single-transmembrane-spanning receptors of cytokines and growth factors have historically proven resistant to the small-molecule screening efforts of the pharmaceutical industry. Advances in combinatorial library approaches to ligand discovery have begun to show success with these targets. There are several recent reports of peptides, derived from randomly assembled collections of L-peptides expressed in recombinant display vectors, that are high-affinity antagonists and even agonists of these receptors. These results indicate that molecules much smaller than the natural protein factors can interact effectively with these receptors, and this may lead the way to the discovery of even smaller nonpeptidic agents.
Dower
W J
WJ
Affymax Research Institute, Palo Alto, CA 92304, USA.
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D011487:Protein Conformation; D018121:Receptors, Cytokine / Q000737:chemistry*; D017978:Receptors, Growth Factor / Q000737:chemistry*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry
D019151:Peptide Library; D018121:Receptors, Cytokine; D017978:Receptors, Growth Factor; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins