title: Further studies toward the stereocontrolled synthesis of silicon-containing peptide mimics.
abstract: Further studies are reported on the utilization of the versatile reaction between chiral sulfinimines and alkyldiphenylsilyl lithium reagents with the goal of preparing a wide range of silanediol-based protease inhibitors. In particular, focus has been placed to demonstrate how a number of genetically encoded amino acid side chains such as serine, threonine, tyrosine, lysine, proline, arginine, aspartate and asparagine might be incorporated into the overall approach. Efforts to apply this synthetic methodology for accessing biologically relevant silanediol dipeptide mimics are also described. This includes the synthesis of a potential inhibitor of the human neutrophil elastase, as well as a diphenylsilane mimic of a hexapeptide fragment of the human islet amyloid polypeptide.
authors.affiliation: Center for Insoluble Protein Structures, Department of Chemistry and Interdisciplinary Nanoscience Center, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark.
authors.forename: Dácil
authors.initials: D
authors.lastname: Hernández
authors.forename: Karl B
authors.initials: KB
authors.lastname: Lindsay
authors.forename: Lone
authors.initials: L
authors.lastname: Nielsen
authors.forename: Tina
authors.initials: T
authors.lastname: Mittag
authors.forename: Klaus
authors.initials: K
authors.lastname: Bjerglund
authors.forename: Stig
authors.initials: S
authors.lastname: Friis
authors.forename: Rasmus
authors.initials: R
authors.lastname: Mose
authors.forename: Troels
authors.initials: T
authors.lastname: Skrydstrup
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D018716:Molecular Mimicry; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012821:Silanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012825:Silicon / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D009842:Oligopeptides; D053491:Proteinase Inhibitory Proteins, Secretory; D012821:Silanes; C475536:silanediol; D019272:Leukocyte Elastase; D012825:Silicon