title: Macrocyclization of Unprotected Peptide Isocyanates.
abstract: A chemistry for the facile two-component macrocyclization of unprotected peptide isocyanates is described. Starting from peptides containing two glutamic acid γ-hydrazide residues, isocyanates can be readily accessed and cyclized with hydrazides of dicarboxylic acids. The choice of a nucleophilic linker allows for the facile modulation of biochemical properties of a macrocyclic peptide. Four cyclic NYAD-1 analogues were synthesized using the described method and displayed a range of biological activities.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 18-563, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Vinogradov
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 18-563, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Zi-Ning
authors.initials: ZN
authors.lastname: Choo
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 18-563, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Kyle A
authors.initials: KA
authors.lastname: Totaro
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 18-563, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Pentelute
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D003500:Cyclization; D003998:Dicarboxylic Acids / Q000737:chemistry; D005971:Glutamates / Q000737:chemistry; D017953:Isocyanates / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003998:Dicarboxylic Acids; D005971:Glutamates; D017953:Isocyanates; C529454:NYAD-1 peptide; D010455:Peptides; D010456:Peptides, Cyclic; C001296:L-glutamic acid-gamma-hydrazide