Synthesis and properties of cyclopropane-derived peptidomimetics.
Small peptides exhibit a wide range of biological activities, but although there are some notable exceptions, they are not generally useful as drugs. This has spurred widespread interest in designing peptidomimetics and introducing them as replacements of portions of native peptides to enhance their biological properties. Special attention has been focused upon rigid replacements because of their potential to preorganize the resulting pseudopeptide in a conformation corresponding to its bound structure. Toward this goal, we invented trisubstituted cyclopropanes as novel peptidomimetics, anticipating that the cyclopropane ring would locally orient the backbone and the corresponding amino acid side chain in the biologically active conformation. Selected aspects of the syntheses and applications of these cyclopropane-derived peptidomimetics are presented in this Account.
Reichelt
Andreas
A
Department of Chemistry and Biochemistry and The Institute of Cellular and Molecular Biology, The University of Texas, Austin, Texas 78712, USA.
Martin
Stephen F
SF
D003521:Cyclopropanes / Q000737:chemistry*; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry
D003521:Cyclopropanes; D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D011480:Protease Inhibitors