title: Direct Fmoc/tert-Bu solid phase synthesis of octamannosyl polylysine dendrimer-peptide conjugates.
abstract: The mannose binding proteins on the surface of the dendritic cells are responsible for capture of pathogens in the early stages of immune response. Conjugation to mannose dendrimers is a rarely explored but potentially powerful strategy for enhancing immunogenicity of synthetic peptides relying on direct delivery to dendritic cells. We describe a general protocol for preparation of pure, monodisperse third-generation mannosylated poly-L-lysine dendrimer-peptide conjugates using direct, machine-assisted Fmoc/t-Bu solid phase peptide synthesis. The glycodendrons were elaborated onto the N- or C-terminus of sequences derived from HIV-1 gp41, SARS-CoV S2 protein, and Influenza Hemagglutinin (consisting of 15-44 residues). The products were obtained in a homogeneous state after cleavage from the resin, deprotection, and a single purification on semipreparative RP-HPLC.
authors.affiliation: Institute of Chemistry, Academia Sinica, 128 Sec. 2, Academia Rd, Nankang, Taipei 11529, Taiwan, Republic of China.
authors.forename: Eric Assen B
authors.initials: EA
authors.lastname: Kantchev
authors.forename: Chung-Chieh
authors.initials: CC
authors.lastname: Chang
authors.forename: Ding-Kwo
authors.initials: DK
authors.lastname: Chang
mesh_terms: D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D050091:Dendrimers / Q000737:chemistry*; D005449:Fluorenes / Q000737:chemistry; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry*; D008968:Molecular Conformation; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry*; D011817:Rabbits; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014759:Viral Envelope Proteins / Q000737:chemistry; D020002:tert-Butyl Alcohol / Q000737:chemistry*
chemical_list: C496789:9-fluorenylmethoxycarbonyl; D050091:Dendrimers; D005449:Fluorenes; D015700:HIV Envelope Protein gp41; D006389:Hemagglutinins, Viral; D010455:Peptides; D014759:Viral Envelope Proteins; C452559:hemagglutinin HA-2 fusogenic peptide, Influenza virus; D011107:Polylysine; D020002:tert-Butyl Alcohol; D008358:Mannose