title: Development of orthogonally protected hypusine for solid-phase peptide synthesis.
abstract: An orthogonally protected hypusine reagent was developed for solid-phase synthesis of hypusinated peptides using the Fmoc/t-Bu protection strategy. The reagent was synthesized in an overall yield of 27% after seven steps from Cbz-Lys-OBzl and (R)-3-hydroxypyrrolidin-2-one. The side-chain protecting groups (Boc and t-Bu) are fully compatible with standard Fmoc chemistry and can be readily removed during the peptide cleavage step. The utility of the reagent was demonstrated by solid-phase synthesis of hypusinated peptides.
authors.affiliation: †Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Aimin
authors.initials: A
authors.lastname: Song
authors.affiliation: †Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tom
authors.affiliation: ‡International Discovery Service Unit, WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: §Department of Protein Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Victoria
authors.initials: V
authors.lastname: Pham
authors.affiliation: ‡International Discovery Service Unit, WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Dajin
authors.initials: D
authors.lastname: Tan
authors.affiliation: ‡International Discovery Service Unit, WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Dengxiong
authors.initials: D
authors.lastname: Zhang
authors.affiliation: ∥Center for Peptide Service, WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Guoyong
authors.initials: G
authors.lastname: Fang
authors.affiliation: ∥Center for Peptide Service, WuXi AppTec (Shanghai) Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: †Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Kurt
authors.initials: K
authors.lastname: Deshayes
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques
chemical_list: C000604157:3-hydroxypyrrolidin-2-one; D000596:Amino Acids; D007202:Indicators and Reagents; D010455:Peptides; D011760:Pyrrolidinones; C100028:hypusine; D008239:Lysine