title: Biaryl-bridged macrocyclic peptides: conformational constraint via carbogenic fusion of natural amino acid side chains.
abstract: A general method for constraining peptide conformations via linkage of aromatic sidechains has been developed. Macrocyclization of suitably functionalized tri-, tetra- and pentapeptides via Suzuki-Miyaura cross-coupling has been used to generate side chain to side chain, biaryl-bridged 14- to 21-membered macrocyclic peptides. Biaryl bridges possessing three different configurations, meta-meta, meta-ortho, and ortho-meta, were systematically explored through regiochemical variation of the aryl halide and aryl boronate coupling partners, allowing fine-tuning of the resultant macrocycle conformation. Suzuki-Miyaura macrocyclizations were successfully achieved both in solution and on solid phase for all three sizes of peptide. This approach constitutes a means of constraining peptide conformation via direct carbogenic fusion of side chains of naturally occurring amino acids such as phenylalanine and tyrosine, and so is complementary to strategies involving non-natural, for example, hydrocarbon, bridges.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, UniteUSA.
authors.forename: Falco-Magnus
authors.initials: FM
authors.lastname: Meyer
authors.forename: James C
authors.initials: JC
authors.lastname: Collins
authors.forename: Brendan
authors.initials: B
authors.lastname: Borin
authors.forename: James
authors.initials: J
authors.lastname: Bradow
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
authors.forename: Chris
authors.initials: C
authors.lastname: Limberakis
authors.forename: Alan M
authors.initials: AM
authors.lastname: Mathiowetz
authors.forename: Laurence
authors.initials: L
authors.lastname: Philippe
authors.forename: David
authors.initials: D
authors.lastname: Price
authors.forename: Kun
authors.initials: K
authors.lastname: Song
authors.forename: Keith
authors.initials: K
authors.lastname: James
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D012996:Solutions; D013237:Stereoisomerism; D014443:Tyrosine / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D010455:Peptides; D010456:Peptides, Cyclic; D012996:Solutions; D014443:Tyrosine; D010649:Phenylalanine