Direct Fmoc/tert-Bu solid phase synthesis of octamannosyl polylysine dendrimer-peptide conjugates.
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.
Kantchev
Eric Assen B
EA
Institute of Chemistry, Academia Sinica, 128 Sec. 2, Academia Rd, Nankang, Taipei 11529, Taiwan, Republic of China.
Chang
Chung-Chieh
CC
Chang
Ding-Kwo
DK
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*
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